William Shakespeare 's sexuality has been the subject of frequent debates. It is known from public records that he married  Anne Hathaway  and had three children with her; scholars have examined their relationship through documents, and particularly through the bequests to her in  his will . Some historians have speculated Shakespeare had affairs with other women, based on contemporaries' written anecdotes of such affairs and sometimes on the " Dark Lady " figure in  his sonnets . Some scholars have argued he was  bisexual , based on analysis of the sonnets; many, including  Sonnet 18 , are love poems addressed to a man (the "Fair Youth"), and contain puns relating to  homosexuality . Whereas, other scholars criticized this view stating that these passages are referring to intense platonic friendship, rather than sexual love. [ 1 ] [ 2 ]  Another explanation is that the poems are not autobiographical but fiction, another of Shakespeare's "dramatic characterization[s]", so that the narrator of the sonnets should not be presumed to be Shakespeare himself. [ 3 ] [ 4 ]


At the age of 18, Shakespeare married the 26-year-old  Anne Hathaway . The  consistory court  of the  Diocese of Worcester  issued a  marriage licence  on 27 November 1582. Two of Hathaway's neighbours posted  bonds  the next day as  surety  that there were no impediments to the marriage. [ 5 ] [ 6 ]  The couple may have arranged the ceremony in some haste, since the Worcester  chancellor  allowed the  marriage banns  to be read once instead of the usual three times. [ 7 ] [ 8 ] [ 9 ]  Hathaway's pregnancy could have been the reason for this. Six months after the marriage, she gave birth to a daughter,   Susanna . [ 10 ]  Twins, son  Hamnet  and daughter  Judith , followed almost two years later. [ 11 ]


Literary historian  Stephen Greenblatt  argues that Shakespeare probably initially loved Hathaway, supporting this by referring to the theory that a passage in one of his sonnets ( Sonnet 145 ) plays off Anne Hathaway's name, saying she saved his life (writing "I hate from hate away she threw/And saved my life, saying 'not you.'"). [ 12 ]  Nevertheless, after only three years of marriage Shakespeare left his family and moved to London. Greenblatt suggests that this may imply that he felt trapped by Hathaway. [ 13 ]  Other evidence to support this belief is that he and Anne were buried in separate (but adjoining) graves and, as has often been noted, Shakespeare's will makes no specific bequest to his wife aside from "the second best bed with the furniture". This may seem like a slight, but many historians contend that the second best bed was typically the marital bed, while the best bed was reserved for guests. [ 14 ]  The poem " Anne Hathaway " by  Carol Ann Duffy  endorses this view of the second best bed, having Anne say: "The bed we loved in was a spinning world of forests, castles, torchlight, clifftops, seas where we would dive for pearls." On the other hand, "In the other bed, the best, our guests dozed on, dribbling their prose". [ 15 ]  A bed missing from an inventory of Anne's brother's possessions (removed in contravention of their father's will) allows the explanation that the item was an heirloom from the Hathaway family that had to be returned. [ 16 ]  The law at the time also stated that the widow of a man was automatically entitled to a third of his estate, so Shakespeare did not need to mention specific bequests in the will. [ 16 ]


While in London, Shakespeare may have had affairs with different women. One anecdote along these lines is provided by a lawyer named  John Manningham , who wrote in his diary that Shakespeare had a brief affair with a woman during a performance of  Richard III . [ 17 ]


Upon a time when Burbage played Richard the Third there was a citizen grew so far in liking with him, that before she went from the play she appointed him to come that night unto her by the name of Richard the Third. Shakespeare, overhearing their conclusion, went before, was entertained and at his game ere Burbage came. Then, message being brought that Richard the Third was at the door, Shakespeare caused return to be made that William the Conqueror was before Richard the Third. [ 18 ]


The Burbage referred to is  Richard Burbage , the star of Shakespeare's company, who is known to have played the title role in  Richard III . While this is one of the few surviving contemporary anecdotes about Shakespeare—it was made in March 1602, a month after Manningham had seen the play [ 19 ] [ 20 ] —some scholars are sceptical of its validity. [ 21 ]  Still, the anecdote suggests that at least one of Shakespeare's contemporaries (Manningham) believed that Shakespeare was attracted to women, even if he was not 'averse to an occasional infidelity to his marriage vows'. [ 22 ]  Indeed, its significance has been developed to affording Shakespeare a preference for "promiscuous women of little beauty and no breeding" in his honest acknowledgement that well-born women are beyond his reach. [ 18 ]


An even less certain reference to an affair is a passage in the poem  Willobie His Avisa , by  Henry Willobie , which refers to Shakespeare's  The Rape of Lucrece  in the line "Shake-speare paints poor Lucrece' rape". Later in the poem there is a section in which "H.W." (Henry Willobie) and "W.S." discuss Willobie's love for "Avisa" in a verse conversation. This is introduced with a short explanatory passage:


W.S., who not long before had tried the courtesy of the like passion, and was now newly recovered ... he [Willobie] determined to see whether it would sort to a happier end for this new actor, than it did for the old player.


The fact that W.S. is referred to as a "player", and is mentioned after a complimentary comment on Shakespeare's poetry has led several scholars to conclude that Willobie is describing a conversation with Shakespeare about love affairs. "W.S." goes on to give Willobie advice about how to win over women. [ 23 ]


Other possible evidence of other affairs are that twenty-six of Shakespeare's  Sonnets  are love poems addressed to a married woman (the so-called ' Dark Lady ').


Shakespeare's sonnets  are cited as evidence of his bisexuality. The poems were initially published, perhaps without his approval, in 1609. [ 24 ]  126 of them appear to be love poems addressed to a young man known as the 'Fair Lord' or 'Fair Youth'; this is often assumed to be the same person as the 'Mr W.H.' to whom the sonnets are dedicated. [ 3 ]  The identity of this figure (if he is indeed based on a real person) is unclear; the most popular candidates are Shakespeare's patrons,  Henry Wriothesley, 3rd Earl of Southampton  and  William Herbert, 3rd Earl of Pembroke , both of whom were considered handsome in their youth. [ 25 ]


Explicit references to sexual acts or physical lust also occur in the Dark Lady sonnets, which suggest that the poet and the Lady are lovers. Nevertheless, there are numerous passages in the sonnets addressed to the Fair Lord that express desire for a younger man. [ 26 ]  In  Sonnet 13 , he is called "dear my love", and  Sonnet 15  announces that the poet is at "war with Time for love of you."  Sonnet 18  asks "Shall I compare thee to a summer's day? / Thou art more lovely and more temperate", [ 27 ]  and in  Sonnet 20  the narrator calls the younger man the "master-mistress of my passion". The poems refer to sleepless nights, anguish and jealousy caused by the youth. In addition, there is considerable emphasis on the young man's beauty: in Sonnet 20, the narrator theorises that the youth was originally a woman with whom  Mother Nature  had fallen in love and, to resolve the dilemma of lesbianism, added a penis ("pricked thee out for women's pleasure"), an addition the narrator describes as "to my purpose nothing". The line can be read literally as a denial of sexual interest. However, given the homoerotic tone of the rest of the sonnet, it could also be meant to appear disingenuous, [ 28 ]  mimicking the common sentiment of would-be seducers: 'it's  you  I want, not your body’. In Sonnet 20, the narrator tells the youth to sleep with women, but to love only him: "mine be thy love and thy love's use their treasure".


In some sonnets addressed to the youth, such as  Sonnet 52 , the erotic  punning  is particularly intense: "So is the time that keeps you as my chest, / Or as the wardrobe which the robe doth hide, / To make some special instant special blest, / By new unfolding his imprisoned pride." In Elizabethan bawdy, 'pride' is a euphemism for penis, especially an erect one. [ 29 ]


Others have countered that these passages could be referring to intense  platonic   friendship , rather than sexual love. In the preface to his 1961 Pelican edition, Douglas Bush writes:


Since modern readers are unused to such ardor in masculine friendship and are likely to leap at the notion of homosexuality (a notion sufficiently refuted by the sonnets themselves), we may remember that  such an ideal , often exalted above the love of women, could exist in real life, from  Montaigne  to  Sir Thomas Browne , and was conspicuous in  Renaissance literature . [ 30 ]


Richard Dutton writes that the Shakespearean scholar  A. L. Rowse  never accepted that the Bard was homosexual to any extent at all, writing that "Shakespeare’s interest in the youth is not at all sexual". Dutton comments:


Rowse’s conviction on this point remained unshaken to his death, which is odd, not least because he himself was widely understood to be homosexual and wrote openly about writers like  Marlowe  and  Wilde . [ 1 ]


Another explanation is that the poems are not autobiographical but fiction, another of Shakespeare's "dramatic characterization[s]", so that the narrator of the sonnets should not be presumed to be Shakespeare himself. [ 3 ] [ 31 ]


In 1640,  John Benson  published a second edition of the sonnets in which he changed most of the pronouns from masculine to feminine so that readers would believe nearly all of the sonnets were addressed to the Dark Lady. Benson's modified version soon became the best-known text, and it was not until 1780 that  Edmond Malone  re-published the sonnets in their original forms. [ 32 ]


The question of the sexual orientation of the sonnets' author was openly articulated in 1780, when  George Steevens , upon reading Shakespeare's description of a young man as his "master-mistress" remarked, "it is impossible to read this fulsome panegyrick, addressed to a male object, without an equal mixture of disgust and indignation". [ 33 ]  Other scholars concurred with  Samuel Taylor Coleridge 's comment, made around 1800, that Shakespeare's love was "pure" and in his sonnets there is "not even an allusion to that very worst of all possible vices". [ 34 ]   Robert Browning , writing of Wordsworth's assertion that "with this key [the Sonnets] Shakespeare unlocked his heart", famously replied in his poem  House , "If so, the less Shakespeare he!" [ 35 ]


Oscar Wilde  addressed the issue of the dedicatee of the sonnets in his 1889 short story " The Portrait of Mr. W. H. " in which he identified Will Hughes, a boy actor in Shakespeare's company, as both "Mr W. H." and the "Fair Youth". [ 36 ]


The controversy continued in the 20th century. By 1944, the Variorum edition of the sonnets contained an appendix with the conflicting views of nearly forty commentators. In the year after "the law in Britain decriminalized homosexual acts between consenting males over twenty-one", the historian G. P. V. Akrigg published the first extended study of the Earl of Southampton, "who he had no doubt was the 'fair youth' of the sonnets." Akrigg wrote, "One is forced to suspect that some element of homosexuality lay at the root of the trouble . . . The love which he felt for Southampton may well have been the most intense emotion of his life." [ 1 ]


Literary theorist  Stephen Greenblatt , in writing about sexuality within Southampton’s world, "assumes that something went on—'whether they only stared longingly at one another or embraced, kissed passionately, went to bed together'". [ 37 ]


Stanley Wells  also addressed the topic in  Looking for Sex in Shakespeare  (2004), arguing that a balance had yet to be drawn between the deniers of any possible homoerotic expression in the sonnets and more recent, liberal commentators who have "swung too far in the opposite direction" and allowed their own sensibilities to influence their understanding. [ 38 ]  One element that complicates the question of Shakespeare's sexuality is that same-sex friendships in the Renaissance were often characterized by shows of affection (e.g., bed sharing, confessions of love) that contemporary readers associate with modern-day sexual relationships. [ 39 ] [ 40 ]


A scholarly dispute on the matter occurred in the letters pages of  The Times Literary Supplement  in 2014. [ 41 ]


In  psychology ,  womb envy   denotes the  envy  that men may feel of the biological functions of the female (pregnancy, childbirth, breastfeeding). The  neo-Freudian  psychiatrist  Karen Horney  (1885–1952) proposed this as an innate male psychological trait. These emotions could fuel the  social  subordination of women, and drive men to succeed in other areas of life, such as business, medicine, law, and politics. [ 1 ] [ 2 ] [ 3 ]  Each term is analogous to the concept of female  penis envy  presented in  Freudian psychology . In this they address the  gender role  social dynamics underlying the "envy and fascination with the female breasts and lactation, with pregnancy and childbearing, and vagina envy [that] are clues and signs of transsexualism and to a femininity complex of men, which is defended against by psychological and sociocultural means". [ 4 ]


Womb envy denotes the envy men may feel towards a woman's role in nurturing and sustaining life. In coining the term, the  Neo-Freudian   psychiatrist   Karen Horney  (1885–1952) proposed that men experience womb envy more powerfully than women experience penis envy, because "men need to disparage women more than women need to disparage men". [ 5 ]  This feeling is stronger in men because they want to live up to the male stereotype of having the upper hand and dominance over everyone. Boehm (1930, p. 457) said that when others have something more that we do not have ourselves then this excites our envy. [ 6 ]  As a  psychoanalyst , Horney considered womb envy a cultural,  psychosocial  tendency, like the concept of penis envy, rather than an innate male psychological trait. [ 1 ]  She believed that it arises when men think they are not in control and powerful in their lives like they thought they were. [ 7 ]


Although Karen Horney is generally credited with originating the idea of "womb envy," especially in her 1926 article "The Flight from Womanhood: The Masculinity-Complex in Women as Viewed by Men and by Women," [ 8 ]  she herself never used the term. One early appearance of the phrase was in  Margaret Mead 's 1949 book,  Male and Female . [ 9 ]  Mead may have coined the term.


Brian Luke, in his book  Brutal: Manhood and the Exploitation of Animals, [ 10 ]  discusses three ways in which men who experience womb envy may respond: by compensating—constructing a realm of exclusively male activity, by revaluing—devaluing the functions specific to women and/or magnifying the functions specific to men, and by appropriation—taking control of female specific functions. [ 10 ]


Luke attributes the coining of this term not to Horney, but to  Eva Kittay . In her 1984 article,  Rereading Freud on 'Femininity' or Why Not Womb Envy? , [ 11 ]  Kittay had posed the question of why there is not a concept analogous to penis envy and offers the term womb envy. [ 11 ]


In  Personality Theories,  Barbara Engler discusses the often unconscious and indirect ways that womb envy manifests. "Womb envy, rather than being openly acknowledged by most males, has often taken subtle and indirect forms, such as rituals of taboo, isolation, and cleansing that have been frequently associated with  menstruation  and childbirth, the need to disparage women, accuse them of witchcraft, belittle their achievements and deny them equal rights." [ 12 ]  Engler also refers to criticism of Horney's theory on the grounds that it equated  womanhood  with  motherhood . [ 12 ]


Discussing the limitations of Horney's broader psychological viewpoint, Bernardo J. Carducci points out the comparative lack of empirical evidence saying, "In comparison to other theorists..., Horney's work has generated very little empirical research among personality psychologists. Although her theoretical ideas were presented in a relatively straightforward manner, they have not stimulated much interest in others to investigate their validity. This may be in part due to the rejection of her ideas by the more traditional and influential Freudian tradition operating at the time." [ 13 ]


In  Eve's Seed  (2000), historian  Robert S. McElvaine  extended Horney's argument that womb envy is a powerful, elementary factor in the psychological  insecurity  suffered by many men. He coined the term  non-menstrual syndrome  (NMS), denoting a man's possible insecurity before the biologic and reproductive traits of woman; thus, womb envy may impel men to define their  identities  in opposition to women. Hence, men who are envious of women's reproductive traits insist that a "real man" must be "not-a-woman", thus they may seek to socially dominate women—what they may or may not do in life—as psychological compensation for what men cannot do biologically. [ 14 ]


Along with womb envy there are other mentions that also discussed on topic of womb envy though not the exact name. Michael Joseph Eisler (1921) wrote it by looking at male pregnancy fantasies, not the direct term of womb envy is mentioned but contributed the male envy of female reproductive physiology was directed towards it.  Boehm  (1930) called it parturition envy instead,  Zilboorg  (1944) called it women envy, and  Phyllis Chesler  (1978) called it uterus envy. [ 6 ]


Vagina envy  denotes the envy males may feel towards females for having a  vagina . In  Psychoanalysis and Male Sexuality  (1966), Hendrik Ruitenbeek relates vagina envy to men's desire to be able to give birth and to urinate  and to  masturbate  in ways  physically  different from those available to men, and that such psychological envy might produce  misogyny  in  neurotic  men. [ 15 ]  Moreover, in  Vagina Envy in Men  (1993), the physician Harold Tarpley elucidates the theoretic differences among the constructs of "vagina envy", "womb envy", "breast envy", and "parturition envy", emotions wherein men suffer envy—"a grudging desire for another's excellence or advantage"—of women's female biologic capabilities of pregnancy, parturition, breast feeding, and of the social-role freedom to physically nurture children. [ 16 ]


The theory of "womb envy" or "vaginal envy" is criticized based on the position that it indicates how the essence of being a woman lies in motherhood. [ 17 ]  There are scholars who point out that the woman defined in terms of her essential maternity reduces her to her gender characteristics and could, hence, be exploited or be defined according to the terms of patriarchal logic and phallocentric impositions. [ 18 ]  Domna Stanton, for instance, drew from  Jacques Derrida 's work to support this argument, [ 18 ]  particularly, the theorist's position that "the maternal, which is metaphorized as total being to substantiate a notion that can combat the paternal, represents only one aspect of potential female difference." [ 19 ]


HIV lymphadenopathy is seen here microscopically in the early phase with follicular hyperplasia at medium power.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Progressive multifocal leukoencephalopathy is caused by infection with the JC papovavirus. Here, small round dark JC viral particles appear in the nucleus of an infected oligodendrocyte in this electron micrograph.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Microscopically, PML lesions appear with perivascular monocytes, astrocytosis with bizarre or enlarged astrocytes (with occasional mitotic figures), and central lipid-laden macrophages. At the periphery of the lesions are large "ballooned" oligodendrocytes infected with JC virus that have enlarged dark pink "ground glass" nuclei containing viral antigen.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Progressive multifocal leukoencephalopathy (PML) affects oligodendrocytes, and cell lysis results in lesions that demonstrate demyelination, as shown here by the Luxol fast blue (LFB) stain in white matter.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Progressive multifocal leukoencephalopathy (PML) appears grossly as irregular areas of granularity in white matter which bear some resemblance to the plaques of demyelination with multiple sclerosis.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Lymphoid interstitial pneumonitis (LIP) is seen here in lung at high power. The mononuclear cells are not malignant.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Lymphoid interstitial pneumonitis (LIP) is seen here in lung at medium power. LIP can appear as interstitial infiltrates of mononuclear cells or as aggregates.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Lymphoid interstitial pneumonitis (LIP) is seen here in lung at medium power. LIP is not seen in adults with AIDS.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


Lymphoid interstitial pneumonitis (LIP) is seen here in lung at low power. LIP can appear in children with AIDS.Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.


At high magnification, this non-Hodgkin's lymphoma infiltrating the cerebrum
is composed of large lymphocytes with occasional mitoses.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Non-Hodgkin's lymphomas seen in the central nervous system with AIDS are essentially clonal expansions of Epstein-Barr virus infected lymphocytes. These lymphomas are high grade (immunoblastic) and agressive, with a poor prognosis. Seen here is the edge of such a lymphoma infiltrating the cerebrum.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Malignant lymphoma is typically high grade in AIDS. Seen here in small intestine are cells of a large cell lymphoma infiltrating the mucosa.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Extranodal malignant lymphoma in AIDS is often multifocal. Seen here in liver are two mass lesions on the cut surface. The color can range from white to tan to red, often intermixed.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Malignant lymphoma is typically extranodal in AIDS. Seen here in small intestine are two mass lesions on the mucosal surface.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Cut sections of this enlarged lymph node involved with high-grade non-Hodgkin's lymphoma in AIDS reveal a "strawberry sundae" appearance with swirls and globs of red in white. This can also be seen with extra-nodal AIDS lymphomas.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Visceral involvement with Kaposi's sarcoma in AIDS is common.  Here are multiple reddish irregular masses in the liver.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Visceral involvement with Kaposi's sarcoma in AIDS is common. Here are multiple reddish nodules seen over the gastric mucosa.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma can also be highlighted with the use of an immunohistochemical stain with antibody to CD34, which stains the cells forming the vascular slits.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma characteristically has hyaline globules, as seen here stained with PAS.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma characteristically has deposits of hemosiderin granules and faint, pale pink hyaline globules, as seen here.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma microscopically produces slit-like vascular spaces in the dermis of the skin with extravasation of red blood cells.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma microscopically produces slit-like vascular spaces in the dermis of the skin, seen here as a nodule.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma microscopically produces slit-like vascular spaces in the dermis of the skin, seen here in the patch stage of KS.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


Kaposi's sarcoma typically produces one or more reddish purple nodules on the skin, as seen here grossly.Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.


A cyst of Isospora belli is present in this acid fast stained preparation from a stool specimen.Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.


Cryptosporidia are seen along the brush border of the intestinal mucosa in this electron micrograph.Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.


Cryptosporidia are best seen in a stool specimen with acid fast staining.Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.


Small blue cryptosporidia line the surface of the small intestinal epithelium shown here.Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.


The major gastrointestinal protozoa (Cryptosporidium, Microsporidium, and Isospora organisms) are compared morphologically in this diagram.Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.


Herpes simplex virus, seen here in the esophagus, infects the squamous epithelium and manifests with multinucleated cells and inclusions.Herpes simplex virus infection with AIDS is most likely to involve the gastrointestinal tract, mainly the esophagus and the perianal region. Herpes zoster infection of the skin can also occur prior to the onset of clinical AIDS. Herpes infections are rarely life-threatening.


Herpes simplex virus often produces sharply demarcated ulcerations in oral, esophageal, or perianal regions. Here is the edge of an ulcer seen microscopically.Herpes simplex virus infection with AIDS is most likely to involve the gastrointestinal tract, mainly the esophagus and the perianal region. Herpes zoster infection of the skin can also occur prior to the onset of clinical AIDS. Herpes infections are rarely life-threatening.


Herpes simplex virus morphology is diagrammed here.Herpes simplex virus infection with AIDS is most likely to involve the gastrointestinal tract, mainly the esophagus and the perianal region. Herpes zoster infection of the skin can also occur prior to the onset of clinical AIDS. Herpes infections are rarely life-threatening.


The free tachyzoites of Toxoplasma gondii are difficult to distinguish by H and E staining, so an immunohistochemical stain can be very helpful. Tachyzoites are seen here in lung.Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.


Toxoplasma gondii infection can also occur in the heart. Here a pseudocyst appears in myocardium.Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.


Toxoplasma gondii infection can result in the formation of pseudocysts, which have the infected cell forming the cyst wall, and the cysts contain bradyzoites. Pseudocysts are seen here in cerebrum in a microglial nodule.Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.


Toxoplasma gondii morphology is diagrammed here.Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.


Toxoplasma gondii infection is most often manifested in the central nervous system. Multiple abscesses that are ring-enhancing with CT scans can be seen. Older abscesses can organize, as shown here grossly in brain.Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.


Spherules of Coccidioides immitis are seen here in liver with H and E staining. Note the thick wall of the sperules containing endospores. One spherule is rupturing to release the endospores, the yeast phase which grows at body temperature.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Coccidioides immitis infection can often be disseminated to multiple organs, though pneumonia is often present because the infection is acquired via the respiratory tract. Spherules are seen here in lung with H and E staining.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Coccidioides immitis morphology is diagrammed here.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Histoplasma capsulatum organisms in macrophages are seen in liver with PAS stain.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Histoplasma capsulatum is often a disseminated infection, and the macrophages containing small yeasts appear in multiple organs, particularly those of the mononuclear phagocyte system (lymph node, liver, spleen, marrow). Here the organisms are seen in liver with H and E stain.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Histoplasma capsulatum may lead to formation of visible granulomas, but they are often small, as shown here in the liver. More often, involvement is diffuse, leading only to organomegaly.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Histoplasma capsulatum morphology is diagrammed here, with appearances by both GMS and PAS staining.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


In cerebrospinal fluid obtained via lumbar puncture, Cryptococcus neoformans organisms are highligted by their surrounding capsule, which is white, with a central rounded pale nucleus. Two cryptococcal organisms are seen here.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Cryptococcus neoformans organisms often lack a capsule, but the nucleus stains well with GMS staining as seen here microscopically in the meninges in a case of cryptococcal meningitis.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Cryptococcus neoformans often produces a pneumonia, because infection is acquired via the respiratory tract. Here, C neoformans organisms have a clear capsule surrounding the pale blue nucleus with H and E staining.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Cryptococcus neoformans morphology is diagrammed here.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Candida albicans is seen here as an invasive process in the esophagus with GMS staining.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Candida albicans is seen here as an invasive process in the esophagus with PAS staining.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Candida albicans is seen here as an invasive process in a bronchus with H and E staining.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Candida albicans morphology is diagrammed here.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Candida infections are common with AIDS, but most often appear as oral thrush, which is a nuisance but not life-threatening. Disseminated infections are uncommon, but here is a rare Candida pneumonia, which resembles a bacterial bronchopneumonia.There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.


Mycobacterium avium complex (MAC) with acid fast stain often has the characteristic appearance shown here with numerous mycobacteria filling macrophages. Such macrophages may be distributed diffusely or in clusters.Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.


Mycobacterium avium complex (MAC) morphology is diagrammed here.Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.


Mycobacterium avium complex (MAC) may produce a grossly visible yellowish-tan cut surface, as seen here in these mesenteric lymph nodes, because the mycobacteria are so numerous.Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.


Mycobacterium avium complex (MAC) may produce grossly visible granulomas, as seen here in the spleen. However, often there is organ enlargement, but no visible granulomas.Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.


Mycobacterium tuberculosis infection of lung is shown here  with numerous red rods seen with acid fast staining.Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.


Mycobacterium tuberculosis infection of lung, with upper lung field granulomatous and cavitary disease shown here, is similar to florid cases in non-AIDS patients.Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.


Immunoperoxidase staining may reveal CMV in some cases where the inclusions are not numerous or characteristic.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


CMV can often be disseminated and involve a variety of organs, though the degree of organ failure from such involvement varies greatly. Seen here is a characteristic inclusion in liver.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


CMV most often involves the adrenal, but this uncommonly leads to major clinical signs or symptoms.  Inclusions can appear in medulla and cortex.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


CMV inclusions in lung are seen here microscopically.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


CMV inclusions in lung are seen here microscopically.  A cell can have more than one inclusion.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


CMV can often produce a pneumonia. Here are CMV inclusions in lung.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


The morphologic appearances of cytomegalovirus are diagrammed here. The cell is so large that in histologic sections, the plane of section may not reveal all or part of the nucleus in every cytomegalic cell, and the cytoplasmic inclusions, though characteristic for CMV, are not always present.Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.


Pneumocystis carinii may have a variety of "atypical" features, including scant foamy exudate and interstitial fibrosis, as seen here microscopically.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


Pneumocystis carinii, often when disseminated and sometimes in the lung as shown here, can produce large areas of the foamy pink exudate that can calcify.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


Disseminated of Pneumocystis carinii has led to splenomegaly, and the masses of exudate produce the lucent areas in spleen seen here with CT scan.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


With dissemination to extrapulmonary sites, Pneumocystis carinii tends to produce foci with prominent calcification, as seen in the kidney here grossly.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


With immunohistochemical stain with antibody to Pneumocystis carinii at high magnification, the brown-red reaction produce is seen highlighting the exudates.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


Pap staining of fluid obtained from bronchoalveolar lavage, bronchial washing, or sputum may reveal a characteristic "foamy body" seen here, which represents the alveolar exudate in Pneumocystis carinii infection.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


The giemsa stain demonstrates the faint bluish dot-like intracystic bodies of Pneumocystis carinii in this cytologic preparation from a bronchoalveolar lavage. This staining technique works best with cytologic smears.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


With giemsa stain at high magnification, the faint bluish dot-like intracystic bodies of Pneumocystis carinii in lung are seen in this cytologic preparation from a bronchoalveolar lavage.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


With Gomori methenamine silver stain at high magnification, the cysts of Pneumocystis carinii in lung have the appearance of crushed ping-pong balls.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


With Gomori methenamine silver stain, Pneumocystis carinii in lung is demonstrated by the appearance of brown to black cysts in the alveolar exudate.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


At low magnification, note the appearance of Pneumocystis carinii in lung with exudate in nearly every alveolus.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


In rare cases, Pneumocystis carinii pneumonia may produce cavitary change, as shown here grossly in lung.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


The appearance of Pneumocystis carinii grossly in lung is shown here.  Note that this is an extensive pneumonia.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


The appearance of Pneumocystis carinii with the Gomori methenamine silver (GMS) stain (which stains the capsule) and the Giemsa stain (which stains up to eight intracystic bodies but not the capsule) is diagrammed here.Pneumocystis jiroveci (formerly carinii) is the most frequent opportunistic infection seen with AIDS. It commonly produces a pulmonary infection but rarely disseminates outside of lung. The most frequent clinical findings in patients with pneumonia are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P jiroveci stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.


The interaction of HIV gp120 with the CD4 receptor is shown here. The chemokine coreceptor in the cell membrane induces a conformational change in gp41 that allows fusion of virus with cell membrane.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.


The life cycle of HIV shown with the points at which pharmacologic agents may block the viral life cycle involving the host cell, including points for inhibition of viral entry, reverse transcriptase, integrase, TAT transcription, protease, and maturation, in this diagram.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.


A schematic representation of the phylogeny of human immunodeficiency virus (HIV) subtypes and simian immunodeficiency virus (SIV) is shown in this diagram. Subtypes of HIV vary in geographic distribution.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.


The genome of the human immunodeficiency virus type 1 (HIV-1) is shown in the schematic diagram above.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.


Human immunodeficiency virus is shown crossing the mucosa of the genital tract to infect CD4+ T-lymphocytes. A Langerhans cell in the epithelium is shown in red in this diagram.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.


Human immunodeficiency virus, once it enters the body, is carried to the lymphoid tissues where both CD4+ T-lymphocytes as well as follicular dendritic cells can become infected, as shown in this diagram.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.


The life cycle of human immunodeficiency virus is diagrammed here. Note that the reverse transcriptase enzyme makes an HIV proviral DNA that is incorporated into the host cell.Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released. The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11. In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.