HIV

This is a good article. Click here for more information.
Page semi-protected
Source: Wikipedia, the free encyclopedia.
(Redirected from
Human immunodeficiency virus
)

Human immunodeficiency viruses
Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions.
Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte
. Multiple round bumps on cell surface represent sites of assembly and budding of virions.
Scientific classificationEdit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Lentivirus
Groups included
Other lentiviruses

The human immunodeficiency viruses (HIV) are two species of

acquired immunodeficiency syndrome (AIDS),[1][2] a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive.[3] Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.[4]

In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids.[5][6] 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.[7][8][9][10] Within these bodily fluids, HIV 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 untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load.[5][6]

HIV infects vital cells in the human immune system, such as

CD8+ cytotoxic lymphocytes that recognize infected cells.[14] 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 the development of AIDS.

Virology

Comparison of HIV species
Species Virulence Infectivity Prevalence Inferred origin
HIV-1 High High Global
Common chimpanzee
HIV-2 Lower Low West Africa Sooty mangabey

Classification

HIV is a member of the

transcribed
, producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from 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,[20] 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 is largely confined to West Africa.[21]

Structure and genome

Diagram of the HIV virion

HIV is similar in structure to other retroviruses. It is roughly spherical

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.[24] The single-stranded RNA 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.[24]

This is, in turn, surrounded by the

glycoprotein (gp) 120, and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope.[25][26] The envelope protein, encoded by 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.[25]

A diagram of the HIV spike protein (green), with the fusion peptide epitope highlighted in red, and a broadly neutralizing antibody (yellow) binding to the fusion peptide

As the sole viral protein on the surface of the virus, the envelope protein is a major target for

HIV vaccine efforts.[27] Over half of the mass of the trimeric envelope spike is N-linked glycans. The density 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.[28][29] 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 a cell surface.[30] 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.[31]

The molecular structure of the viral spike has now been determined by

radical replacement of an amino acid) in gp41.[34] 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.[35] Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120, which act to suppress the immune response to target epitopes.[36]

Structure of the RNA genome of HIV-1

The RNA genome consists of at least seven structural landmarks (

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 the structural proteins for new virus particles.[24] 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.[24]

The two

G2/M. The nef protein (p27) down-regulates CD4 (the major viral receptor), as well as the MHC class I and class II molecules.[40][41][42]

Nef also interacts with

frameshift in the gag-pol reading frame required to make functional pol.[24]

Tropism

Diagram of the immature and mature forms of HIV

The term

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.[25][43]

Macrophage-tropic (M-tropic) strains of HIV-1, or non-

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[44]) replicate in primary CD4+ T cells as well as in macrophages and use the α-chemokine receptor, CXCR4, for entry.[45][46][47]

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

myeloid dendritic cells,[48] 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.

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.

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 the whole organism. However, a selection process[further explanation needed] leads to a predominant transmission of the R5 virus through this pathway.[50][51][52] 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.[53] These variants then replicate more aggressively with heightened virulence that causes rapid T cell depletion, immune system collapse, and opportunistic infections that mark the advent of AIDS.[54] 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.[3] Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be 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.[55][56]

HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution to

commensal organism. Having achieved a low pathogenicity, over time, variants that are more successful at transmission will be selected.[57]

Replication cycle

The HIV replication cycle

Entry to the cell

Mechanism of viral entry: 1. Initial interaction between gp120 and CD4. 2. Conformational change in gp120 allows for secondary interaction with CXCR4. 3. The distal tips of gp41 are inserted into the cellular membrane. 4. gp41 undergoes significant conformational change; folding in half and forming coiled-coils. This process pulls the viral and cellular membranes together, fusing them.

The HIV virion enters

T cells by 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.[58][59]

Entry to the cell begins through interaction of the trimeric envelope complex (

virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1.[60] The gp160 spike contains binding domains for both CD4 and chemokine receptors.[58][59]

The first step in fusion involves the high-affinity attachment of the CD4 binding domains of

gp120 to CD4. Once gp120 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.[58][59] This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane.[58][59] Repeat sequences in gp41, HR1, and HR2 then interact, causing 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.[58][59]

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.[58][failed verification] During 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

FEZ-1, which occurs naturally in neurons, is believed to prevent the infection of cells by HIV.[62]

Clathrin-mediated endocytosis

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

clathrin-mediated endocytosis of HIV-1 has also been reported and was recently suggested to constitute the only route of productive entry.[63][64][65][66][67]

Replication and transcription

double-stranded DNA

Shortly after the viral capsid enters the cell, an

drug resistance or allow 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.[69] Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus. The integration of the viral DNA into the host cell's genome is carried out by another viral enzyme called integrase.[68]

The integrated viral DNA may then lie dormant, in the latent stage of HIV infection.[68] To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF-κB (nuclear factor kappa B), which is upregulated when T cells become activated.[70] This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection.

During viral replication, the integrated DNA

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 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.[71] The labile gRNA dimer has been also reported to achieve 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.[72]

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 the HIV protein-coding sequences is translated.[73]

Mature HIV mRNAs are exported from the nucleus into the

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.[74] Some of these full-length RNAs function as mRNAs that are translated to produce the structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles.[75]
HIV-1 and HIV-2 appear to package their RNA differently.[76][77] HIV-1 will bind to any appropriate RNA.[78] HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself.[79]

Recombination

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 the two genomes can occur.[80][81] 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 the genetic information that is transmitted from parental to progeny genomes.[81]

Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral therapy.[82] 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 is unknown how often such mixed packaging occurs under natural conditions.[83]

Bonhoeffer et al.[84] 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[80] 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 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, the generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching.[84]

HIV-1 infection causes

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.[86]
suggested that recombination by viruses is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit.

Assembly and release

HIV assembling on the surface of an infected macrophage. The HIV virions have been marked with a green fluorescent tag and then viewed under a fluorescent microscope.

The final step of the viral cycle, assembly of new HIV-1 virions, begins at the

gp120.[87] 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 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.[88]
Only mature virions are then able to infect another cell.

Spread within the body

Animation demonstrating cell-free spread of HIV

The classical process of infection of 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".

lymphoid tissues, where CD4+ T cells are densely packed and likely to interact frequently.[89] Intravital imaging studies have supported the concept of the HIV virological synapse in vivo.[93] The many dissemination mechanisms available to HIV contribute to the virus' ongoing replication in spite of anti-retroviral therapies.[89][94]

Genetic variability

The phylogenetic tree of the SIV and HIV

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 1010 virions every day, coupled with a high mutation rate of approximately 3 x 10−5 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase.[95][96][97]

This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day.

DNA sequence that is a recombinant between the two parental genomes.[95] This recombination is most obvious when it occurs between subtypes.[95]

The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of 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,[98] which is present at high levels in the host's blood, but evokes only a mild immune response,[99] does not cause the development of simian AIDS,[100] and does not undergo the extensive mutation and recombination typical of HIV infection in humans.[101]

In contrast, when these strains infect species that have not adapted to SIV ("heterologous" or similar hosts such as

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 is more likely, leading to immunodeficiency.[103][104]

Three groups of HIV-1 have been identified on the basis of differences in the envelope (env) region: M, N, and O.

gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006.[109]

HIV-2's closest relative is SIVsm, 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.[111][112]

Diagnosis

A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of untreated HIV infection; any particular individual's disease course may vary considerably.
  CD4+ T cell count (cells per µL)
  HIV RNA copies per mL of plasma

Many HIV-positive people are unaware that they are infected with the virus.[113] For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion is even lower in rural populations.[113] Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results.[113] Again, this proportion is even lower in rural health facilities.[113] 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.[114]

HIV-1 testing is initially done using 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.[116]

HIV deaths in 2014 excluding the U.S.:[117]

  Nigeria (15.76%)
  South Africa (12.51%)
  India (11.50%)
  Tanzania (4.169%)
  Mozambique (4.061%)
  Zimbabwe (3.49%)
  Cameroon (3.09%)
  Indonesia (3.04%)
  Kenya (2.98%)
  Uganda (2.97%)
  Malawi (2.94%)
  DR Congo (2.17%)
  Ethiopia (2.11%)
  Other (29.21%)

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.[115] In addition, 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.[118] The chance of a false-positive result in a standard two-step testing protocol is estimated to be about 1 in 250,000 in a low risk population.[119] Testing post-exposure is recommended immediately and then at six weeks, three months, and six months.[120]

The latest recommendations of the US

Centers for Disease Control and Prevention (CDC) show that HIV testing must start with an immunoassay combination test for HIV-1 and HIV-2 antibodies and p24 antigen
. A negative result rules out HIV exposure, while a positive one must be followed by an HIV-1/2 antibody differentiation immunoassay to detect which antibodies are present. This gives rise to four possible scenarios:

Research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Many governments and research institutions participate in HIV/AIDS research. This research includes behavioral

accelerated aging effects
.

Treatment and transmission

The management of HIV/AIDS normally includes the use of multiple

antiretroviral drugs. In many parts of the world, HIV has become a chronic condition in which progression to AIDS
is increasingly rare.

HIV latency, and the consequent viral reservoir in CD4+ T cells, dendritic cells, as well as macrophages, is the main barrier to eradication of the virus.[19][123]

Although HIV is highly virulent, transmission does not occur through sex when an HIV-positive person has a consistently undetectable viral load (<50 copies/ml) due to anti-retroviral treatment. This was first argued by the Swiss Federal Commission for AIDS/HIV in 2008 in the Swiss Statement, though the statement was controversial at the time.[124][125] However, following multiple studies, it became clear that the chance of passing on HIV through sex is effectively zero where the HIV-positive person has a consistently undetectable viral load; this is known as U=U, "Undetectable=Untransmittable", also phrased as "can't pass it on".[126][127] The studies demonstrating U=U are: Opposites Attract,[128] PARTNER 1,[129] PARTNER 2,[5][130] (for male-male couples)[131] and HPTN052[132] (for heterosexual couples) when "the partner living with HIV had a durably suppressed viral load."[131] In these studies, couples where one partner was HIV positive and one partner was HIV negative were enrolled and regular HIV testing completed. In total from the four studies, 4097 couples were enrolled over four continents and 151,880 acts of condomless sex were reported; there were zero phylogenetically linked transmissions of HIV where the positive partner had an undetectable viral load.[133] Following this, the U=U consensus statement advocating the use of "zero risk" was signed by hundreds of individuals and organisations, including the US CDC, British HIV Association and The Lancet medical journal.[134] The importance of the final results of the PARTNER 2 study were described by the medical director of the Terrence Higgins Trust as "impossible to overstate", while lead author Alison Rodger declared that the message that "undetectable viral load makes HIV untransmittable ... can help end the HIV pandemic by preventing HIV transmission.[135] The authors summarised their findings in The Lancet as follows:[5]

Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.[5]

This result is consistent with the conclusion presented by

Journal of the American Medical Association, that U=U is an effective HIV prevention method when an undetectable viral load is maintained.[6][131]

Genital herpes (HSV-2) reactivation in those infected with the virus have an associated increase in CCR-5 enriched CD4+ T cells as well as inflammatory dendritic cells in the submucosa of the genital skin. Tropism of HIV for CCR-5 positive cells explains the two to threefold increase in HIV acquisition among persons with genital herpes. Daily antiviral (e.g. acyclovir) medication does not reduce the sub-clinical post reactivation inflammation and therefore does not confer reduced risk of HIV acquisition.[136][137]

History

Discovery

The first news story on "an exotic new disease" appeared May 18, 1981, in the gay newspaper New York Native.[138]

AIDS was first clinically observed in 1981 in the United States.

NYU School of Medicine studied gay men developing a previously rare skin cancer called Kaposi's sarcoma (KS).[141][142] Many more cases of PJP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak.[143] The earliest retrospectively described case of AIDS is believed to have been in Norway beginning in 1966.[144]

In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example,

gay community,[147] it was realized that the term GRID was misleading and AIDS was introduced at a meeting in July 1982.[151] By September 1982 the CDC started using the name AIDS.[152]

In 1983, two separate research groups led by American

physical weakness, two classic symptoms of primary HIV infection. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV).[143] As these two viruses turned out to be the same, in 1986 LAV and HTLV-III were renamed HIV.[156]

Another group working contemporaneously with the Montagnier and Gallo groups was that of Jay A. Levy at the University of California, San Francisco. He independently discovered the AIDS virus in 1983 and named it the AIDS associated retrovirus (ARV).[157] This virus was very different from the virus reported by the Montagnier and Gallo groups. The ARV strains indicated, for the first time, the heterogeneity of HIV isolates and several of these remain classic examples of the AIDS virus found in the United States.[158]

Origins

Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa, and are believed to have transferred to humans (a process known as zoonosis) in the early 20th century.[159][160]

HIV-1 appears to have originated in southern

chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes troglodytes).[161][162] The closest relative of HIV-2 is SIVsmm, a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in littoral West Africa (from southern Senegal to western Côte d'Ivoire).[21] New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.[163]

HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three groups of the virus, M, N, and O.[164]

HIV-1

There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.[165] However, SIV is a weak virus, and it is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into HIV.[166] Furthermore, due to its relatively low person-to-person transmission rate, it can only spread throughout the population in the presence of one or more high-risk transmission channels, which are thought to have been absent in Africa prior to the 20th century.

Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to c. 1910.

sexually transmitted infection resulting in genital ulcers. Early 1900s colonial cities were notable for their high prevalence of prostitution and genital ulcers to the degree that as of 1928 as many as 45% of female residents of eastern Leopoldville (currently Kinshasa) were thought to have been prostitutes and as of 1933 around 15% of all residents of the same city were infected by one of the forms of syphilis.[168]

The earliest, well-documented case of HIV in a human dates back to 1959 in the Belgian Congo.[169] The virus may have been present in the United States as early as the mid- to late 1960s, as a sixteen-year-old male named Robert Rayford presented with symptoms in 1966 and died in 1969.[170]

An alternative and likely complementary hypothesis points to the widespread use of unsafe medical practices in Africa during years following World War II, such as unsterile reuse of single-use syringes during mass vaccination, antibiotic, and anti-malaria treatment campaigns.[166][171][172] Research on the timing of most recent common ancestor for HIV-1 groups M and O, as well as on HIV-2 groups A and B, indicates that SIV has given rise to transmissible HIV lineages throughout the twentieth century.[173] The dispersed timing of these transmissions to humans implies that no single external factor is needed to explain the cross-species transmission of HIV. This observation is consistent with both of the two prevailing views of the origin of the HIV epidemics, namely SIV transmission to humans during the slaughter or butchering of infected primates, and the colonial expansion of sub-Saharan African cities.[173]

See also

References

  1. PMID 8493571
    .
  2. .
  3. ^ .
  4. ^ UNAIDS, WHO (December 2007). "2007 AIDS epidemic update" (PDF). p. 16.
  5. ^
    PMID 31056293
    .
  6. ^ .
  7. .
  8. .
  9. PMID 18941560. Archived from the original
    on 6 November 2008.
  10. ^ Public Domain This article incorporates text from this source, which is in the public domain: "Preventing Mother-to-Child Transmission of HIV". HIV.gov. May 15, 2017. Retrieved December 8, 2017.
  11. PMID 20598938
    .
  12. .
  13. .
  14. .
  15. ^ International Committee on Taxonomy of Viruses (2002). "61.0.6. Lentivirus". National Institutes of Health. Archived from the original on October 14, 2006. Retrieved February 28, 2006.{{cite web}}: CS1 maint: unfit URL (link)
  16. ^ International Committee on Taxonomy of Viruses (2002). "61. Retroviridae". National Institutes of Health. Archived from the original on October 2, 2006. Retrieved February 28, 2006.{{cite web}}: CS1 maint: unfit URL (link)
  17. PMID 8280406
    .
  18. .
  19. ^ .
  20. .
  21. ^ .
  22. .
  23. .
  24. ^ a b c d e f g Various (2008). HIV Sequence Compendium 2008 Introduction (PDF). Retrieved March 31, 2009.
  25. ^
    S2CID 4518241
    .
  26. .
  27. ^ National Institute of Health (June 17, 1998). "Crystal structure of key HIV protein reveals new prevention, treatment targets" (Press release). Archived from the original on February 19, 2006. Retrieved September 14, 2006.
  28. PMID 26972002
    .
  29. .
  30. .
  31. .
  32. .
  33. .
  34. .
  35. .
  36. .
  37. .
  38. .
  39. .
  40. .
  41. .
  42. .
  43. .
  44. ^ .
  45. ^ .
  46. ^ Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996). "Identification of a major co-receptor for primary isolates of HIV-1". Nature. 381 (6584): 661–6.
    S2CID 37973935
    .
  47. ^ Feng Y, Broder CC, Kennedy PE, Berger EA (1996). "HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor". Science. 272 (5263): 872–7.
    S2CID 44455027
    .
  48. .
  49. .
  50. .
  51. .
  52. .
  53. .
  54. .
  55. .
  56. .
  57. ]
  58. ^ .
  59. ^ .
  60. ^ .
  61. ^ .
  62. .
  63. .
  64. .
  65. .
  66. .
  67. .
  68. ^ .
  69. ^ "IV. Viruses> F. Animal Virus Life Cycles > 3. The Life Cycle of HIV". Doc Kaiser's Microbiology Home Page. Community College of Baltimore County. January 2008. Archived from the original on July 26, 2010.
  70. PMID 11160127
    .
  71. .
  72. .
  73. .
  74. .
  75. .
  76. .
  77. .
  78. .
  79. .
  80. ^ .
  81. ^ .
  82. .
  83. .
  84. ^ .
  85. .
  86. .
  87. .
  88. ^ Gelderblom HR (1997). "Fine structure of HIV and SIV" (PDF). In Los Alamos National Laboratory (ed.). HIV sequence compendium. Los Alamos National Laboratory. pp. 31–44.
  89. ^
    PMID 25837979
    .
  90. ^ .
  91. .
  92. .
  93. .
  94. .
  95. ^ .
  96. .
  97. .
  98. ^ .
  99. .
  100. ^ Kurth R, Norley S (1996). "Why don't the natural hosts of SIV develop simian AIDS?". The Journal of NIH Research. 8: 33–37.
  101. PMID 1896460
    .
  102. .
  103. ^ .
  104. .
  105. .
  106. ^ Carr JK, Foley BT, Leitner T, Salminen M, Korber B, McCutchan F (1998). "Reference sequences representing the principal genetic diversity of HIV-1 in the pandemic" (PDF). In Los Alamos National Laboratory (ed.). HIV sequence compendium. Los Alamos, New Mexico: Los Alamos National Laboratory. pp. 10–19.
  107. S2CID 12536801
    .
  108. .
  109. ^ .
  110. ^ Smith L (August 3, 2009). "Woman found carrying new strain of HIV from gorillas". The Independent. Retrieved November 27, 2015.
  111. PMID 20643738
    .
  112. .
  113. ^ a b c d Kumaranayake L, Watts C (2001). "Resource allocation and priority setting of HIV/AIDS interventions: addressing the generalized epidemic in sub-Saharan Africa". Journal of International Development. 13 (4): 451–466. .
  114. ^ Kleinman S (September 2004). "Patient information: Blood donation and transfusion". Uptodate. Archived from the original on April 12, 2008.
  115. ^
    PMID 11718472
    .
  116. .
  117. ^ "Country Comparison :: HIV/AIDS - Deaths". The World Factbook, Central Intelligence Agency. Archived from the original on April 30, 2017. Retrieved November 22, 2015.
  118. from the original on March 22, 2024.
  119. from the original on October 11, 2021.
  120. from the original on November 28, 2023.
  121. ^ "Quick Reference Guide—Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations" (PDF). Centers for Disease Control and Prevention. New York State Department of Health. June 27, 2014. pp. 1–2. Archived from the original (PDF) on March 2, 2017. Retrieved April 13, 2017.
  122. ^ "HIV Treatment: FDA-Approved HIV Medicines". AIDSinfo. Archived from the original on February 23, 2017. Retrieved October 7, 2016.
  123. PMID 34586875
    .
  124. ^ Swiss National AIDS Commission (October 15, 2016). "The Swiss statement". HIV i-Base. Retrieved April 2, 2019.
  125. PMID 26824882
    .
  126. .
  127. ^ "Can't Pass It On". Terrence Higgins Trust. 2019. Archived from the original on April 7, 2019. Retrieved April 2, 2019.
  128. S2CID 51702998
    .
  129. .
  130. ^ Rodger A( (July 2018). Risk of HIV transmission through condomless sex in MSM couples with suppressive ART: The PARTNER2 Study extended results in gay men. AIDS2018: 22nd International AIDS Conference. Amsterdam, the Netherlands. Retrieved April 2, 2019.
  131. ^ a b c Hoffman H (January 10, 2019). "The science is clear: with HIV, undetectable equals untransmittable" (Press release). National Institutes of Health. National Institute of Allergy and Infectious Diseases. Retrieved May 3, 2019. NIAID Director Anthony S. Fauci, M.D., and colleagues summarize results from large clinical trials and cohort studies validating U=U. The landmark NIH-funded HPTN 052 clinical trial showed that no linked HIV transmissions occurred among HIV serodifferent heterosexual couples when the partner living with HIV had a durably suppressed viral load. Subsequently, the PARTNER and Opposites Attract studies confirmed these findings and extended them to male-male couples. ... The success of U=U as an HIV prevention method depends on achieving and maintaining an undetectable viral load by taking ART daily as prescribed.
  132. PMID 27424812
    .
  133. NAM / Aidsmap
    )
  134. ^ "Consensus statement: Risk of Sexual Transmission of HIV from a Person Living with HIV who has an Undetectable Viral Load". Prevention Access Campaign. July 21, 2016. Retrieved April 2, 2019. Note: When the statement and list of endorsements was retrieved, it had last been updated on 23 August 2018 and included "over 850 organizations from nearly 100 countries."
  135. ^ Boseley S, Devlin H (May 3, 2019). "End to AIDS in sight as huge study finds drugs stop HIV transmission". The Guardian. Retrieved May 3, 2019.
  136. PMID 19648930
    .
  137. .
  138. ^ "On this day". News & Record. May 18, 2020. pp. 2A.
  139. ]
  140. from the original on April 22, 2009.
  141. .
  142. .
  143. ^ .
  144. . Retrieved June 9, 2016.
  145. .
  146. ^ .
  147. ^ .
  148. ^ Altman LK (May 11, 1982). "New homosexual disorder worries health officials". The New York Times. Retrieved August 31, 2011.
  149. JSTOR 3397566
    .
  150. ^ "Making Headway Under Hellacious Circumstances" (PDF). American Association for the Advancement of Science. July 28, 2006. Archived from the original (PDF) on June 24, 2008. Retrieved June 23, 2008.
  151. ^ Kher U (July 27, 1982). "A Name for the Plague". Time. Archived from the original on March 7, 2008. Retrieved March 10, 2008.
  152. PMID 6815471
    .
  153. .
  154. ^ "The 2008 Nobel Prize in Physiology or Medicine - Press Release". www.nobelprize.org. Retrieved January 28, 2018.
  155. ^ Crewdson J (May 30, 1991). "GALLO ADMITS FRENCH DISCOVERED AIDS VIRUS". Chicago Tribune. Retrieved April 25, 2020.
  156. .
  157. .
  158. .
  159. .
  160. .
  161. .
  162. .
  163. .
  164. .
  165. .
  166. ^ .
  167. .
  168. ^ .
  169. .
  170. ^ Kolata G (October 28, 1987). "Boy's 1969 death suggests AIDS invaded U.S. several times". The New York Times. Retrieved February 11, 2009.
  171. S2CID 17783758
    .
  172. ^ McNeil D Jr (September 16, 2010). "Precursor to H.I.V. was in monkeys for millennia". The New York Times. Archived from the original on January 3, 2022. Retrieved September 17, 2010. Dr. Marx believes that the crucial event was the introduction into Africa of millions of inexpensive, mass-produced syringes in the 1950s. ... suspect that the growth of colonial cities is to blame. Before 1910, no Central African town had more than 10,000 people. But urban migration rose, increasing sexual contacts and leading to red-light districts.
  173. ^
    PMID 19412344
    .

Further reading

External links