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122-407: Yet this remarkably warm and welcoming dive is about as far removed from The Groucho, or the rarefied environs of Soho House as it's possible to get... a hive of hangovers, teeming with sozzled actors, out-of-work soap stars, comedians, musicians, writers and assorted hacks, tumbling over one another in a delirious heap, as opposed to engaging in anything so cynical as 'networking'. Mostly because, after

244-493: A long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell. The Psi element is involved in viral genome packaging and recognized by gag and rev proteins. The SLIP element ( TTTTTT ) is involved in the frameshift in the gag - pol reading frame required to make functional pol . The term viral tropism refers to

366-427: A Man , singer Boy George discusses how he had felt an affinity towards Crisp during his childhood, as they faced similar problems as young homosexual people living in homophobic surroundings. In 1991, a documentary about Crisp, Resident Alien , was released by Greycat Films. Crisp was then the subject of the play Resident Alien , by Tim Fountain , which starred his friend Bette Bourne . The play opened in 1999 at

488-535: A cell by a virion can be called "cell-free spread" to distinguish it from a more recently recognized process called "cell-to-cell spread". In cell-free spread (see figure), virus particles bud from an infected T cell, enter the blood or extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread, for which two pathways have been described. Firstly, an infected T cell can transmit virus directly to

610-481: A cell surface. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to, or are adapted to cope with, these envelope glycans. The molecular structure of the viral spike has now been determined by X-ray crystallography and cryogenic electron microscopy . These advances in structural biology were made possible due to

732-768: A century old, with a decade off for good behaviour, proved prophetic . He was cremated with a minimum of ceremony as he had requested, and his ashes were flown back to his personal assistant and travel companion Phillip Ward in New York. He bequeathed his rights in three books to his respective collaborators: Phillip Ward for Crisp's final book The Last Word and the book And One More Thing (formerly titled Dusty Answers ); Guy Kettelhack for The Wit and Wisdom of Quentin Crisp and John Hofsess for Manners from Heaven . From his remaining literary estate (including The Naked Civil Servant), he bequeathed all future UK-only income (but not

854-488: A companion book to The Last Word: An Autobiography , again edited by Ward and Watts. This book contains material that the editors believed did not fit into The Last Word . In And One More Thing , Crisp primarily shares his views on other people, their lives and their opinions, from flapper girls to Monica Lewinsky , and from the British Royal Family to Walt Disney . Also included are his collected poems,

976-705: A condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype . In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood , pre-ejaculate , semen , and vaginal fluids . Non-sexual transmission can occur from an infected mother to her infant during pregnancy , during childbirth by exposure to her blood or vaginal fluid, and through breast milk . Within these bodily fluids, HIV

1098-482: A distant town and run a knitting wool shop and no one would ever have known my secret. I would have joined the real world and it would have been wonderful." Crisp died of a heart attack on 21 November 1999, at age 90, while staying at the home of a friend in Chorlton-cum-Hardy , Manchester, on the eve of a nationwide revival of his one-man show. A humorous pact he had made with Penny Arcade to live to be

1220-548: A feminine appearance to a degree that shocked contemporary Londoners and provoked " gay-bashing " assaults. By his own account, Crisp was "effeminate" from an early age, resulting in his being teased while at Kingswood House School in Epsom , Surrey, from which he won a scholarship to Denstone College , Uttoxeter , Staffordshire, in 1922. After leaving school in 1926, Crisp studied journalism at King's College London , but failed to graduate in 1928, going on to take art classes at

1342-414: A few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection. Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time. The chance of a false-positive result in a standard two-step testing protocol

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1464-539: A first-floor flat at 129 Beaufort Street, Chelsea , a bed-sitting room that he occupied until he emigrated to the United States in 1981. In the intervening years, he never attempted any housework, writing famously in his memoir The Naked Civil Servant : "After the first four years the dirt doesn't get any worse." Crisp left his job as an engineer's tracer in 1942 to become a model in life classes in London and

1586-524: A hub of late night drinking and debauchery for artists, actors, comedians, producers, writers and journalists. Karaoke was banned, the jukebox abolished, and Huggett became a centrepiece of flamboyance, renowned for giving impromptu performances of showtunes. Among the Phoenix clientele were the crime novelist Martina Cole , singer Lady Gaga , comedian Noel Fielding and the actors Jude Law , Keira Knightley and John Hurt . Huggett flatly refused entry to

1708-451: A human host cell when the newly formed virus particle buds from the cell. The viral envelope contains proteins from the host cell and relatively few copies of the HIV envelope protein, which consists of a cap made of three molecules known as glycoprotein (gp) 120 , and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope. The envelope protein, encoded by

1830-574: A key step in the progression to AIDS. A number of studies with subtype B-infected individuals have determined that between 40 and 50 percent of AIDS patients can harbour viruses of the SI and, it is presumed, the X4 phenotypes. HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution to West Africa . The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) may assist

1952-613: A more stable conformation following the NC binding, in which both the DIS and the U5:AUG regions of the gRNA participate in extensive base pairing. RNA can also be processed to produce mature messenger RNAs (mRNAs). In most cases, this processing involves RNA splicing to produce mRNAs that are shorter than the full-length genome. Which part of the RNA is removed during RNA splicing determines which of

2074-407: A new direction: that of performer and tutor. He devised a one-man show and began touring the country with it. The first half of the show was an entertaining monologue loosely based on his memoirs, while the second half was a question-and-answer session with Crisp picking the audience's written questions at random and answering them in an amusing manner. After the success of the film, his autobiography

2196-474: A night in the Phoenix, you'd be hard-pressed to remember anybody's name. Through it all, Maurice reigned supreme (or like a Supreme), dancing, pouting and gliding around the hubbub in a vast and never-ending collection of legendary waistcoats to a piped soundtrack of Fiddler on the Roof, offering advice, comfort, support, and an inexhaustible supply of friendship and queenly asides. In Quentin Crisp 's phrase, "one of

2318-447: A number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4 T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4 T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to

2440-557: A short documentary, Uncle Denis? , at the 23rd London Lesbian & Gay Film Festival . The film uses interviews with family and previously unseen home movie footage. In collaboration with Crisperanto (The Quentin Crisp Archives) curator Philip Ward, Goycoolea also created an installation entitled 'Personal Effects' at the 2010 MIX NYC , New York City, which recreated Crisp's New York apartment using his personal effects and included home video footage. In 2013, with curator Ward,

2562-464: A strain of SIV found in sooty mangabees. Since HIV-1 is derived from SIVcpz, and HIV-2 from SIVsm, the genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIVsm. Many HIV-positive people are unaware that they are infected with the virus. For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion

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2684-558: A target T cell via a virological synapse . Secondly, an antigen-presenting cell (APC), such as a macrophage or dendritic cell, can transmit HIV to T cells by a process that either involves productive infection (in the case of macrophages) or capture and transfer of virions in trans (in the case of dendritic cells). Whichever pathway is used, infection by cell-to-cell transfer is reported to be much more efficient than cell-free virus spread. A number of factors contribute to this increased efficiency, including polarised virus budding towards

2806-600: A television sequel to The Naked Civil Servant was broadcast. Entitled An Englishman in New York , the production documented Crisp's later years in Manhattan. Thirty-four years after his first award-winning performance as Crisp, John Hurt returned to play him again. Other co-stars included Denis O'Hare as Phillip Steele (an amalgam character based on Crisp's friends Phillip Ward and Tom Steele), Jonathan Tucker as artist Patrick Angus , Cynthia Nixon as Penny Arcade , and Swoosie Kurtz as Connie Clausen . The production

2928-409: A woman. But, later on, you realise that you have to live in the real world, and that you are not a woman. You are only in some senses 'effeminate,' or 'feminine,' and you must learn to make this compromise - to live in a world where, statistically, you are a man, whatever you may think about yourself." At the age of 90 Crisp said in his book The Last Word that he had come to the conclusion that he

3050-460: Is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit. The final step of the viral cycle, assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi apparatus where it is cleaved by furin resulting in

3172-516: Is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane. Repeat sequences in gp41, HR1, and HR2 then interact, causing

3294-424: Is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results. Again, this proportion is even lower in rural health facilities. Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV. HIV-1 testing

3416-464: Is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on human glycoproteins that are secreted or present on

3538-399: Is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate. If the result of either duplicate test is reactive,

3660-447: Is largely confined to West Africa . HIV is similar in structure to other retroviruses. It is roughly spherical with a diameter of about 120  nm , around 100,000 times smaller in volume than a red blood cell . It is composed of two copies of positive- sense single-stranded RNA that codes for the virus' nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24 . The single-stranded RNA

3782-612: Is more likely, leading to immunodeficiency. Three groups of HIV-1 have been identified on the basis of differences in the envelope ( env ) region: M, N, and O. Group M is the most prevalent and is subdivided into eight subtypes (or clades ), based on the whole genome, which are geographically distinct. The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in

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3904-561: Is present as both free virus particles and virus within infected immune cells . Research has shown (for both same-sex and opposite-sex couples) that HIV is not contagious during sexual intercourse without a condom if the HIV-positive partner has a consistently undetectable viral load . HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4 T cells), macrophages , and dendritic cells . HIV infection leads to low levels of CD4 T cells through

4026-412: Is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase , proteases , ribonuclease and integrase . A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle. This is, in turn, surrounded by the viral envelope , that is composed of the lipid bilayer taken from the membrane of

4148-534: Is unknown how often such mixed packaging occurs under natural conditions. Bonhoeffer et al. suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of

4270-457: The AIDS crisis , inviting censure from gay activists including human-rights campaigner Peter Tatchell . During his teen years, he worked briefly as a rent boy . He then spent thirty years as a professional model for life classes in art colleges. The interviews he gave about his unusual life attracted great curiosity, and he was soon sought after for his personal views on social manners and

4392-638: The African green monkey (SIVagm) and sooty mangabey (SIVsmm) are thought to have a long evolutionary history with their hosts. These hosts have adapted to the presence of the virus, which is present at high levels in the host's blood, but evokes only a mild immune response, does not cause the development of simian AIDS, and does not undergo the extensive mutation and recombination typical of HIV infection in humans. In contrast, when these strains infect species that have not adapted to SIV ("heterologous" or similar hosts such as rhesus or cynomologus macaques ),

4514-577: The Arctic Monkeys because they looked "too scruffy" - despite their latest single being at the top of the British charts at the time. The writer Bryony Gordon remembers Huggett "barred an acquaintance of mine for six months due to drunken misbehaviour. When my friend ventured back at the end of his ban, he was warmly embraced by Maurice who asked where on earth he had been, and by the way, would he like free membership." Another regular recalls "amid

4636-796: The Bush Theatre in London; in 2001, it transferred to the New York Theatre Workshop where it won two Obies (for performance and design). In 2002, it won a Herald Angel (Best Actor) at the Edinburgh Festival ; subsequent productions have been seen across the US and Australia. The 1981 synthpop song No G.D.M by German electro band Gina X Performance is dedicated to Crisp. The song The Ballad of Jack Eric Williams (and Other Three-Named Composers) from William Finn 's 2003 song-cycle Elegies refers to him. In 2009

4758-544: The CCR5-Δ32 mutation are resistant to infection by the R5 virus, as the mutation leaves HIV unable to bind to this co-receptor, reducing its ability to infect target cells. Sexual intercourse is the major mode of HIV transmission. Both X4 and R5 HIV are present in the seminal fluid , which enables the virus to be transmitted from a male to his sexual partner . The virions can then infect numerous cellular targets and disseminate into

4880-584: The Home Counties . Crisp wanted to call his book I Reign in Hell , a reference to Milton 's Paradise Lost ("Better to reign in Hell, than serve in Heaven"), but his agent insisted on The Naked Civil Servant , an insistence that later gave him pause when he offered the manuscript to Tom Maschler of Jonathan Cape on the same day that Desmond Morris delivered The Naked Ape . The Naked Civil Servant

5002-726: The Museum of Arts and Design in Manhattan staged a three-month retrospective on Crisp, entitled Ladies and Gentlemen, Mr. Quentin Crisp . The retrospective consisted of free screenings of interviews, one man shows, documentaries and other recorded media. In 2014 Mark Farrelly's solo performance Quentin Crisp: Naked Hope debuted at the Edinburgh Festival, before transferring to the St. James's Theatre in London and subsequently touring. It depicts Crisp at his Chelsea flat in

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5124-569: The Regent Street Polytechnic . Around this time, Crisp began visiting the cafés of Soho , his favourite being The Black Cat in Old Compton Street , meeting other young gay men and rent boys , and experimenting with make-up and women's clothes . For six months, he worked as a prostitute; in a 1998 interview, he said he was looking for love, but found only degradation, a reflection he had previously expressed in

5246-445: The adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the target cell membrane and the release of the HIV capsid into the cell. Entry to the cell begins through interaction of the trimeric envelope complex ( gp160 spike) on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4 , but others are known to interact) on

5368-517: The copyrights , which are managed by Ward, and belong to Ward, literary agent Stedman Mays, and writer Mary Tahan) to the two men he considered to have had the greatest influence on his career: his long-time agent Richard Gollner, and his first agent Donald Carroll. In the two years before his death (1997–1999), Crisp had been compiling a work that was initially to be titled The Dusty Answers with Philip Ward. Crisp and Ward developed material for this book through many hours of recorded interviews, which

5490-421: The gag polyproteins still need to be cleaved into the actual matrix, capsid and nucleocapsid proteins. This cleavage is mediated by the packaged viral protease and can be inhibited by antiretroviral drugs of the protease inhibitor class. The various structural components then assemble to produce a mature HIV virion. Only mature virions are then able to infect another cell. The classical process of infection of

5612-514: The microtubule -based transport to the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated into a host chromosome. HIV can infect dendritic cells (DCs) by this CD4-CCR5 route, but another route using mannose-specific C-type lectin receptors such as DC-SIGN can also be used. DCs are one of the first cells encountered by the virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T cells when

5734-403: The phylogenetic tree representing the lineage of the M group of HIV-1. Co-infection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and

5856-426: The telephone directory . He saw it as his duty to converse with anyone who called him, saying "If you don't have your name in the phone book, you're stuck with your friends. How will you ever enlarge your horizons?" He answered the phone with the phrase: "Yes, Lord?", or "Oh yes?", in a querulous tone of voice. His openness to strangers extended to accepting dinner invitations from almost anyone. While he expected that

5978-438: The α -chemokine receptor, CXCR4 , for entry. Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able to use both CCR5 and CXCR4 as co-receptors for viral entry. The α -chemokine SDF-1 , a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down-regulating the expression of CXCR4 on the surface of HIV target cells. M-tropic HIV-1 isolates that use only

6100-427: The β -chemokine receptor, CCR5 , for entry and are thus able to replicate in both macrophages and CD4 T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4 cells become depleted in

6222-468: The 1960s and performing his one-man show thirty years later. In the 2016 Ghostbusters reboot , Bill Murray explicitly based the dress style of his character (Martin Heiss) on Crisp. In his 2020 autobiography Confess , Rob Halford of Judas Priest identifies Crisp as having been a hero of his. When the then closeted Halford had first seen The Naked Civil Servant in 1975, he had been impressed by

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6344-721: The 1968 World in Action interview, which aired on television in 1971. Crisp left home to move to the centre of London at the end of 1930, and after dwelling in a succession of flats, found a bed-sitting room in Denbigh Street, Pimlico , where he "held court with London's brightest and roughest characters." His 'outlandish' appearance—he wore bright make-up, dyed his long hair crimson, painted his fingernails and wore sandals to display his painted toe-nails—brought admiration and curiosity from some quarters, but generally attracted hostility and violence from strangers passing him in

6466-587: The CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that use both, X4R5. However, the use of co-receptors alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection and HIV can also infect a subtype of myeloid dendritic cells , which probably constitute a reservoir that maintains infection when CD4 T cell numbers have declined to extremely low levels. Some people are resistant to certain strains of HIV. For example, people with

6588-405: The DIS (dimerization initiation signal) hairpin is exposed. The formation of the gRNA dimer is mediated by a 'kissing' interaction between the DIS hairpin loops of the gRNA monomers. At the same time, certain guanosine residues in the gRNA are made available for binding of the nucleocapsid (NC) protein leading to the subsequent virion assembly. The labile gRNA dimer has been also reported to achieve

6710-419: The HIV env gene, allows the virus to attach to target cells and fuse the viral envelope with the target cell's membrane releasing the viral contents into the cell and initiating the infectious cycle. As the sole viral protein on the surface of the virus, the envelope protein is a major target for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans . The density

6832-441: The HIV protein-coding sequences is translated. Mature HIV mRNAs are exported from the nucleus into the cytoplasm , where they are translated to produce HIV proteins, including Rev . As the newly produced Rev protein is produced it moves to the nucleus, where it binds to full-length, unspliced copies of virus RNAs and allows them to leave the nucleus. Some of these full-length RNAs function as mRNAs that are translated to produce

6954-570: The HIV virological synapse in vivo . The many dissemination mechanisms available to HIV contribute to the virus' ongoing replication in spite of anti-retroviral therapies. HIV differs from many viruses in that it has very high genetic variability . This diversity is a result of its fast replication cycle , with the generation of about 10 virions every day, coupled with a high mutation rate of approximately 3 x 10 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase. This complex scenario leads to

7076-526: The LTR promoter acting by binding the TAR RNA element. The TAR may also be processed into microRNAs that regulate the apoptosis genes ERCC1 and IER3 . The rev protein (p19) is involved in shuttling RNAs from the nucleus and the cytoplasm by binding to the RRE RNA element. The vif protein (p23) prevents the action of APOBEC3G (a cellular protein that deaminates cytidine to uridine in

7198-611: The Phoenix Artist Club, formerly Shuttleworth's at The Phoenix or "Shuts", in the mid-1990s, located in a basement beneath the Phoenix Theatre on the Charing Cross Road . The basement was originally used as a rehearsal room and dressing room for the theatre, but had been converted into a bar and restaurant during the 1970s. Under his ownership, it acquired extensive refurbishment. The Phoenix became

7320-433: The U.S.: Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations. In addition,

7442-409: The adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process,

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7564-423: The advent of AIDS. HIV-positive patients acquire an enormously broad spectrum of opportunistic infections, which was particularly problematic prior to the onset of HAART therapies; however, the same infections are reported among HIV-infected patients examined post-mortem following the onset of antiretroviral therapies. Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be

7686-403: The animals develop AIDS and the virus generates genetic diversity similar to what is seen in human HIV infection. Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with increased mortality and AIDS-like symptoms in its natural host. SIVcpz appears to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to

7808-535: The basis of tape recordings made of Crisp's dictations, and edited by Ward and Watts. Whereas The Naked Civil Servant made Crisp famous, and How To Become A Virgin detailed that fame and his life in New York, The Last Word was written as a goodbye to the world, with Crisp knowing the end was near. In it he recounts several previously untold stories from his life, walks the reader through his journey from obscurity, reflects on his philosophy and gender identity. In January 2019, MB Books published And One More Thing ,

7930-592: The cell as new virus particles that will begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus 3 (HTLV-III). HIV-1 is more virulent and more infective than HIV-2, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2

8052-470: The cell types a virus infects. HIV can infect a variety of immune cells such as CD4 T cells , macrophages , and microglial cells . HIV-1 entry to macrophages and CD4 T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells' membrane and also with chemokine co-receptors . Macrophage-tropic (M-tropic) strains of HIV-1, or non- syncytia -inducing strains (NSI; now called R5 viruses ) use

8174-459: The collapse of the extracellular portion of gp41 into a hairpin shape. This loop structure brings the virus and cell membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid. After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell. During

8296-742: The cultivation of style. His one-man stage show was a long-running hit both in Britain and America, and he also appeared in films and on television. Crisp defied convention by criticising both gay liberation and Diana, Princess of Wales . Denis Charles Pratt was born in Sutton , Surrey , on 25 December 1908, the fourth child of solicitor Spencer Charles Pratt (1871–1931) and former governess Frances Marion Pratt (née Phillips; 1873–1960). His elder siblings were Katherine (1901–1976), Gerald (1902–1983) and Lewis (1907–1968). He changed his name to Quentin Crisp in his twenties after leaving home, and expressed

8418-447: The development of AIDS. HIV is a member of the genus Lentivirus , part of the family Retroviridae . Lentiviruses have many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period . Lentiviruses are transmitted as single-stranded , positive- sense , enveloped RNA viruses . Upon entry into

8540-577: The development of stable recombinant forms of the viral spike by the introduction of an intersubunit disulphide bond and an isoleucine to proline mutation ( radical replacement of an amino acid) in gp41. The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike, but also display the same degree of immature glycans as presented on the native virus. Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120, which act to suppress

8662-430: The film Orlando . Although he found the role taxing, he won acclaim for a dignified and touching performance. Crisp next had an uncredited cameo in the 1993 AIDS drama Philadelphia . He accepted some other small bit parts and cameos, such as a pageant judge in 1995's To Wong Foo, Thanks for Everything! Julie Newmar . Crisp's last role was in an independent film, American Mod (1999), while his last full-feature film

8784-628: The film and Crisp. Halford came out, in an MTV interview, on 4 February 1998. In 1999, Halford attended San Diego Pride with his partner, Thomas. While there, Halford met Crisp, and got a book signed by him ('To Rob, from Quentin'). According to Halford, he continues to treasure the signed book. Halford views himself as a rock version of Crisp, and refers to himself as the "stately homo of heavy metal". HIV The human immunodeficiency viruses ( HIV ) are two species of Lentivirus (a subgroup of retrovirus ) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS),

8906-431: The generation of many variants of HIV in a single infected patient in the course of one day. This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens,

9028-576: The generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching. HIV-1 infection causes chronic inflammation and production of reactive oxygen species . Thus, the HIV genome may be vulnerable to oxidative damage , including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod et al. suggested that recombination by viruses

9150-552: The genetic information that is transmitted from parental to progeny genomes. Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral therapy . Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It

9272-679: The host would pay for dinner, Crisp did his best to "sing for his supper" by regaling his host with wonderful stories and yarns, much as he did in his theatrical performances. Crisp continued to perform his one-man show, published books on the importance of contemporary manners as a means of social inclusion (as opposed to etiquette, which he claimed is socially exclusive), and supported himself by accepting social invitations and writing film reviews and columns for UK and US magazines and newspapers. He said that provided one could exist on peanuts and champagne, one could quite easily live by going to every cocktail party , premiere and first night to which one

9394-415: The immune response to target epitopes. The RNA genome consists of at least seven structural landmarks ( LTR , TAR , RRE , PE, SLIP, CRS, and INS), and nine genes ( gag , pol , and env , tat , rev , nef , vif , vpr , vpu , and sometimes a tenth tev , which is a fusion of tat , env and rev ), encoding 19 proteins. Three of these genes, gag , pol , and env , contain information needed to make

9516-521: The integrated DNA provirus is transcribed into RNA. The full-length genomic RNAs (gRNA) can be packaged into new viral particles in a pseudodiploid form. The selectivity in the packaging is explained by the structural properties of the dimeric conformer of the gRNA. The gRNA dimer is characterized by a tandem three-way junction within the gRNA monomer, in which the SD and AUG hairpins , responsible for splicing and translation respectively, are sequestered and

9638-422: The lead role of Baron Frankenstein , and who in 1987 wrote the song " Englishman in New York " for and about Crisp. Crisp also appeared on the television show The Equalizer in the 1987 episode "First Light", and as the narrator of director Richard Kwietniowski 's short film Ballad of Reading Gaol (1988), based on the poem by Oscar Wilde . Four years later, he was cast in a lead role, and got top billing, in

9760-425: The low-budget independent film Topsy and Bunker: The Cat Killers , playing the door-man of a flea-bag hotel in a run-down neighbourhood, quite like the one he lived in. Director Thomas Massengale reportedly said that Crisp was a delight to work with. The 1990s were his most prolific decade as an actor, as more and more directors offered him roles. In 1992 he was persuaded by Sally Potter to play Elizabeth I in

9882-478: The opening night of his one-man show, An Evening with Quentin Crisp , at The Intar Theatre on Forty-Second Street in New York City (produced by John Glines of The Glines organisation). In an interview with CBC in 1977, upon being queried about whether he desired to be a woman, Crisp stated: "Well, I suppose when I was a child, when I lived almost entirely in a dreamworld, I suppose I thought of myself as

10004-410: The patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system . In the tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus. T-tropic strains of HIV-1, or syncytia -inducing strains (SI; now called X4 viruses ) replicate in primary CD4 T cells as well as in macrophages and use

10126-407: The racket. She knew that royal marriages have nothing to do with love. You marry a man and you stand beside him on public occasions and you wave and for that you never have a financial worry until the day you die." Following her death in 1997 , he commented that it was perhaps her "fast and shallow" lifestyle that led to her demise: "She could have been Queen of England [ sic ] - and she

10248-406: The remaining 5.3% were composed of other subtypes and CRFs. Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes. The existence of a fourth group, "P", has been hypothesised based on a virus isolated in 2009. The strain is apparently derived from gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006. HIV-2's closest relative is SIVsm,

10370-425: The reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes. This recombination is most obvious when it occurs between subtypes. The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of

10492-432: The script for his Alternative Christmas message broadcast on Britain's Channel 4 in 1993, and the script of his one-man show An Evening With Quentin Crisp . Sting dedicated his song " Englishman in New York " (1987) to Crisp, who had jokingly remarked "that he looked forward to receiving his naturalisation papers so that he could commit a crime and not be deported." In late 1986 Sting visited Crisp in his apartment and

10614-519: The single-stranded viral DNA and/or interferes with reverse transcription ). The vpr protein (p14) arrests cell division at G2/M . The nef protein (p27) down-regulates CD4 (the major viral receptor), as well as the MHC class I and class II molecules. Nef also interacts with SH3 domains . The vpu protein (p16) influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called

10736-412: The site of cell-to-cell contact, close apposition of cells, which minimizes fluid-phase diffusion of virions, and clustering of HIV entry receptors on the target cell towards the contact zone. Cell-to-cell spread is thought to be particularly important in lymphoid tissues , where CD4 T cells are densely packed and likely to interact frequently. Intravital imaging studies have supported the concept of

10858-673: The specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person. HIV deaths in 2014 excluding

10980-486: The stately homos of England". The son of a builder, Huggett worked as a bank clerk before joining American Express in London's Haymarket, working for the Keith Prowse ticket agency in 1969 at The Dorchester hotel. After a period working for Pan Am , Huggett lived in pre-revolution Tehran to handle incoming tours for Air Express . According to The Daily Telegraph "one night he looked out from his room to see

11102-632: The streets running red. He called the BBC and gave a dramatic account. Only later did he discover the truth. The first targets of the Islamic fundamentalists were wine cellars, and the streets had been running not with blood but with red wine." He returned to London on the last flight out of Tehran, and obtained a publican's licence. He then managed the Players' Theatre beneath the arches at Charing Cross station . Opened in 1988 by John Mahoney, Huggett acquired

11224-549: The streets. Crisp attempted to join the British army at the outbreak of the Second World War , but was rejected and declared exempt by the medical board on the grounds that he was "suffering from sexual perversion". He remained in London during the 1941 Blitz , stocked up on cosmetics, purchased five pounds of henna and later paraded through the streets during the black-out, picking up G.I.s . In 1940, he moved into

11346-556: The structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles. HIV-1 and HIV-2 appear to package their RNA differently. HIV-1 will bind to any appropriate RNA. HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself. Two RNA genomes are encapsidated in each HIV-1 particle (see Structure and genome of HIV ). Upon infection and replication catalyzed by reverse transcriptase, recombination between

11468-496: The structural proteins for new virus particles. For example, env codes for a protein called gp160 that is cut in two by a cellular protease to form gp120 and gp41. The six remaining genes, tat , rev , nef , vif , vpr , and vpu (or vpx in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease. The two tat proteins (p16 and p14) are transcriptional transactivators for

11590-702: The swirl of tottering A-listers and communal singing, Huggett framed strict house rules. Anyone moving furniture, for example, would prompt him to grab his microphone and to command: "Don’t touch the props! Leave the props alone!”" Huggett died after a short illness in London in December 2011. Those at his bedside reported his death was accompanied to the soundtrack of Man of La Mancha , one of his favourite musicals. Quentin Crisp Quentin Crisp (born Denis Charles Pratt ; ( 1908-12-25 ) 25 December 1908 – ( 1999-11-21 ) 21 November 1999)

11712-427: The target cell surface. Gp120 binds to integrin α 4 β 7 activating LFA-1 , the central integrin involved in the establishment of virological synapses , which facilitate efficient cell-to-cell spreading of HIV-1. The gp160 spike contains binding domains for both CD4 and chemokine receptors. The first step in fusion involves the high-affinity attachment of the CD4 binding domains of gp120 to CD4. Once gp120

11834-413: The target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded enzyme, reverse transcriptase , that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded enzyme, integrase , and host co-factors . Once integrated,

11956-468: The truth. If it's confusing for you, think how confusing it has been for me these past ninety years. The only thing in my life I have wanted and didn't get was to be a woman. It will be my life's biggest regret. If the operation had been available and cheap when I was young, say when I was twenty-five or twenty-six, I would have jumped at the chance. My life would have been much simpler as a result. I would have told nobody. Instead, I would have gone to live in

12078-414: The two HIV envelope glycoproteins, gp41 and gp120 . These are transported to the plasma membrane of the host cell where gp41 anchors gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. The budded virion is still immature as

12200-484: The two genomes can occur. Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle

12322-570: The viral DNA into the host cell's genome is carried out by another viral enzyme called integrase . The integrated viral DNA may then lie dormant, in the latent stage of HIV infection. To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF- κ B (nuclear factor kappa B), which is upregulated when T cells become activated. This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection. During viral replication,

12444-536: The virus in its adaptation to avoid innate restriction factors present in host cells. Adaptation to use normal cellular machinery to enable transmission and productive infection has also aided the establishment of HIV-2 replication in humans. A survival strategy for any infectious agent is not to kill its host, but ultimately become a commensal organism. Having achieved a low pathogenicity, over time, variants that are more successful at transmission will be selected. The HIV virion enters macrophages and CD4 T cells by

12566-425: The virus is captured in the mucosa by DCs. The presence of FEZ-1 , which occurs naturally in neurons , is believed to prevent the infection of cells by HIV. HIV-1 entry, as well as entry of many other retroviruses, has long been believed to occur exclusively at the plasma membrane. More recently, however, productive infection by pH -independent, clathrin-mediated endocytosis of HIV-1 has also been reported and

12688-463: The virus may become latent , allowing the virus and its host cell to avoid detection by the immune system, for an indeterminate amount of time. The virus can remain dormant in the human body for up to ten years after primary infection; during this period the virus does not cause symptoms. Alternatively, the integrated viral DNA may be transcribed , producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from

12810-403: The virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the antisense cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus . The integration of

12932-540: The virus. This virus has also lost a function of the nef gene that is present in most SIVs. For non-pathogenic SIV variants, nef suppresses T cell activation through the CD3 marker. Nef 's function in non-pathogenic forms of SIV is to downregulate expression of inflammatory cytokines , MHC-1 , and signals that affect T cell trafficking. In HIV-1 and SIVcpz, nef does not inhibit T-cell activation and it has lost this function. Without this function, T cell depletion

13054-475: The whole organism. However, a selection process leads to a predominant transmission of the R5 virus through this pathway. In patients infected with subtype B HIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants that can infect a variety of T cells through CXCR4. These variants then replicate more aggressively with heightened virulence that causes rapid T cell depletion, immune system collapse, and opportunistic infections that mark

13176-458: Was HomoHeights (also released as Happy Heights , 1996). He was chosen by Channel 4 to deliver the first Alternative Christmas Speech , a counterpoint to the Queen's Christmas speech , in 1993. Crisp remained fiercely independent and unpredictable into old age. He caused controversy and confusion in the gay community by jokingly calling AIDS "a fad", and homosexuality "a terrible disease". He

13298-507: Was transgender . "Having labelled myself homosexual and having been labelled as such by the wider world, I have effectively lived a 'gay' life for most of my years. Consequently, I can relate to gay men because I have more or less been one for so long in spite of my actual fate being that of a woman trapped in a man's body. I refer to myself as homosexual without thinking because of how I have lived my life. If you are reading this and are gay, think of me as one of your own even though you now know

13420-522: Was a theatre-filling humourist; in 1978, his one-man show sold out London's Duke of York's Theatre . He then took the show to New York. His first stay in the Hotel Chelsea coincided with a fire, a robbery, and the death of Nancy Spungen . Crisp decided to move to New York permanently and, in 1981, found a small apartment at 46 East 3rd Street in Manhattan's East Village . As he had done in London, Crisp allowed his telephone number to be listed in

13542-422: Was an English raconteur , whose work in the public eye included a memoir of his life and various media appearances. Before becoming well known, he was an artist's model , hence the title of his most famous work, The Naked Civil Servant . He afterwards became a gay icon due to his flamboyant personality, fashion sense, and wit. His iconic status was occasionally controversial due to his remarks about subjects like

13664-687: Was close to the end of his life, though he continued to make public appearances, and in June of that year he was one of the guest entertainers at the second Pride Scotland festival in Glasgow. In 1997 Crisp was crowned king of the Beaux-Arts Ball run by the Beaux Arts Society. He presided alongside Queen Audrey Kargere, Prince George Bettinger and Princess Annette Hunt. In December 1998 he celebrated his ninetieth birthday, performing

13786-425: Was continually in demand from journalists requiring a sound-bite, and throughout the 1990s his commentary was sought on any number of topics. Crisp was a stern critic of Diana, Princess of Wales , and her attempts to gain public sympathy following her divorce from Prince Charles . He stated: "I always thought Diana was such trash and got what she deserved. She was Lady Diana before she was Princess Diana, so she knew

13908-691: Was filmed in New York in August 2008 and completed in London in October 2008. The film was directed by British director Richard Laxton , written by Brian Fillis, produced by Amanda Jenks and made its premiere at the Berlinale (the Berlin International Film Festival) in early February 2009, before being shown on television later that year. That same year, Crisp's great-nephew, academic and film-maker Adrian Goycoolea, premiered

14030-477: Was invited. Crisp also acted on television and in films. He made his debut as a film actor in the Royal College of Art 's low-budget production of Hamlet (1976). Crisp played Polonius in the 65-minute adaptation of Shakespeare 's play, alongside Helen Mirren , who played both Ophelia and Gertrude . He appeared in the 1985 film The Bride , which brought him into contact with Sting , who played

14152-471: Was looking for a metaphor. Quentin is a hero of mine, someone I know very well. He is gay and he was gay at a time in history when it was dangerous to be so. He had people beating up on him on a daily basis, largely with the consent of the public." Crisp was the subject of a photographic portrait by Herb Ritts and was also chronicled in Andy Warhol 's diaries. In his 1995 autobiography Take It Like

14274-513: Was necessary because Crisp had lost the use of his left hand and he was unable to use a typewriter or computer. The resulting manuscript remained unpublished for eighteen years after Crisp's death, because Ward found it emotionally difficult to transcribe Crisp's words. A chance meeting with Laurence Watts, who interviewed Ward for Pink News , led them to co-edit Crisp's remaining work. On 21 November 2017, MB Books published The Last Word: An Autobiography , written by Crisp's friend, Philip Ward, on

14396-495: Was published in 1968 to generally good reviews, although it initially only sold 3,500 copies. Crisp was then approached by the documentary film maker Denis Mitchell to be the subject of a 1968 short film in which he discussed his life and lifestyle. The documentary aired on British television in 1971. In 1975, the television version of The Naked Civil Servant was broadcast on British and US television, making actor John Hurt , and Crisp, into stars. This success launched Crisp in

14518-448: Was recently suggested to constitute the only route of productive entry. Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow

14640-532: Was reprinted; Gay News commented that it should have been published posthumously (Crisp said that this was their polite way of telling him to drop dead). Gay rights campaigner Peter Tatchell said he had met Crisp in 1974, and alleged that he was not sympathetic to the Gay Liberation movement of the time. Tatchell said Crisp quipped: "What do you want liberation from? What is there to be proud of? I don't believe in rights for homosexuals." By now Crisp

14762-428: Was swanning about Paris with Arabs. What disgraceful behaviour! Going about saying she wanted to be the queen of hearts. The vulgarity of it is so overpowering." In 1995 he was among the many people interviewed for The Celluloid Closet , a historical documentary addressing how Hollywood films have depicted homosexuality. In his third volume of memoirs, Resident Alien , published in the same year, Crisp stated that he

14884-419: Was told over dinner, and over the next three days, what life had been like for a homosexual man in the largely homophobic Great Britain of the 1920s to the 1960s. Sting was both shocked and fascinated and decided to write the song. It includes the lines: It takes a man to suffer ignorance and smile, Be yourself no matter what they say. Sting says, "Well, it's partly about me and partly about Quentin. Again, I

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