AIDS origin

  HIV, the infectious agent of AIDS, is thought to have originated in non-human primates in sub-Saharan Africa and transferred to humans during the 20th century. The epidemic officially began on 5 June 1981.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-2 may have originated from the Sooty Mangabey (Cercocebus atys), an Old World monkey of Guinea-Bissau, Gabon, and Cameroon.^[1] HIV-1 is more virulent. It is easily transmitted and is the cause of the majority of HIV infections globally. HIV-2 is less transmittable and is largely confined to West Africa. HIV-1 is the species described below.

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Likely spread from animal to human populations

A variety of theories exist explaining the transfer of HIV to humans, but no single hypothesis is unanimously accepted, and the topic remains controversial.

Cameroon chimpanzees hypothesis

The most widely accepted theory is so called 'Hunter' Theory according to which transference from ape to human most likely occurred when a human was bitten by an ape or was cut while butchering one, and the human became infected.^[2] Researchers announced in May 2006 that HIV most likely originated in wild chimpanzees in the southeastern rain forests of Cameroon (modern East Province) ^{[3] [4]} rather than in Kinshasa, Democratic Republic of Congo (formerly Zaire), as had previously been believed. Seven years of research and 1,300 chimpanzee genetic samples led Dr. Beatrice Hahn of the University of Alabama, Birmingham, to identify chimpanzee communities near Cameroon's Sanaga River as the most likely originators. ^[5]

Calculating based on a fixed mutation rate, the jump from chimpanzee to human likely occurred during the French colonial period (1919–1960).

Oral polio vaccine hypothesis

Main article: OPV AIDS hypothesis

Freelance journalist Tom Curtis discussed this controversial possibility for the origin of HIV/AIDS in a 1992 Rolling Stone magazine article. He put forward what is now known as the OPV AIDS hypothesis, which suggests that AIDS was inadvertently caused in the late 1950s in the Belgian Congo by Hilary Koprowski's research into a polio vaccine.^[6] Although subsequently Rolling Stone published a clarification^[7] and paid US$1 in damages^[8] following legal action by Koprowski, the Rolling Stone article motivated another freelance journalist, Edward Hooper, to probe more deeply into this subject. Hooper's research resulted in his publishing a 1999 book, The River, in which he alleged that an experimental oral polio vaccine prepared using chimpanzee kidney tissue was the route through which simian immunodeficiency virus (SIV) crossed into humans to become HIV, thus starting the human AIDS pandemic.^[9]

This theory is contradicted by an analysis of genetic mutation in primate lentivirus strains that estimates the origin of the HIV-1 strain to be around 1930, with 95% certainty of it lying between 1910 and 1950.^[10]While few scientists have questioned the fundamental soundness of the phylogenetic approach employed -- some have questioned the validity of the associated molecular clock mechanism for accurately gauging the passage of time without specific corroborating data,^[11] as in this case.

Edward Hooper rejects the dates calculated using a fixed mutation rate on the basis that phylogenetic dating of "the most recombinogenic organisms known to medical science", immunodeficiency viruses, is "inherently incapable of making any allowance for recombination". ^[12][9]

In February 2000 one of the original developers of the polio vaccine, Philadelphia based Wistar Institute, found a vial of the original vaccine used in the vaccination program. It was analyzed in April 2001, and no traces of either HIV-1 or SIV were found in the sample.^[13] A second analysis showed that only macaque monkey kidney cells, which cannot be infected with SIV or HIV, were used to produce the vaccine.^[14] While the analysis was done on only one vial of vaccine, some scientists have concluded that the polio vaccine theory of the origins of HIV is not possible. ^{[2] [6]}

The hypothesis that oral polio vaccine was involved in the origin of AIDS has been investigated and widely rejected by the scientific community, as a large mass of available evidence contradicts it.^{[15][16][17][18][19][20][21]}

Method of spread

After the initial transfer of HIV from a non-human primate to humans, the virus ultimately spread via contact among humans to the rest of the world. Since a cross species jump is most likely the origin of HIV, and since HIV became a true epidemic, transmissible from human to human, then the following conditions were needed:

1. A large human population,
2. A large nearby population of the appropriate host animal,
3. An infectious pathogen in the host animal, that eventually produces a mutation that can spread from animal to human,
4. Interaction between the species to transmit enough of it to humans to establish a human foothold, which may take millions of individual exposures,
5. A mutation of same pathogen that can spread from human to human,
6. Some method that allows the pathogen to disperse widely. This prevents the infection from "burning out" by either killing off its human hosts or provoking immunity in a local population of humans.

Such requirements existed in the remote past with smallpox, and also with the 20th century Spanish Flu, despite Spanish Flu's New World origin at Fort Riley, Kansas (there the animal reservoir seems to have been two species, chickens and pigs, which were of Old World origin.)

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent and more easily transmitted. HIV-1 is the source of the majority of HIV infections throughout the world, while HIV-2 is less easily transmitted and is largely confined to West Africa.^[22]

Both species of the virus (HIV-1 and HIV-2) are believed to have originated in West-Central Africa and jumped species (zoonosis) from a non-human primate to humans. HIV-1 evolved from a Simian Immunodeficiency Virus (SIV_cpz) found in the chimpanzee subspecies Pan troglodytes troglodytes.^[23] DNA sequencing indicates that HIV-1 (group M) entered the human population in the early 20th century, probably sometime between 1915 and 1941.^[24][25] HIV-2 crossed species from a different strain of SIV, this one found in sooty mangabeys (an Old World monkey) of Guinea-Bissau.^[26]

SIVs in non-human primates tend to cause non-fatal disease. Comparison of the gene sequence of SIV with HIV should therefore give us information about the factors necessary to cause disease in humans. The factors that determine the virulence of HIV as compared to most SIVs are only now being elucidated. Non-human SIVs contain a nef gene that down-regulates CD3, CD4, and MHC class I expression; most non-human SIV's therefore do not induce immunodeficiency; the HIV nef gene however has lost its ability to down-regulate CD3, which results in the immune activation and apoptosis that is characteristic of chronic HIV infection.^[27]

History of known cases and spread

1955-1957: British printer (incorrectly reported as an AIDS death)

The oldest documented possible case of the then-unknown syndrome was thought to have been detected in 1959, when a 25-year-old British printer who had traveled in the navy between 1955 and 1957 (but apparently not to Africa), sought help at the Royal Infirmary of Manchester, England. He reported to have been suffering from puzzling symptoms, among them purplish skin lesions, for nearly two years. His condition had taken a turn for worse during Christmas 1958, when he started suffering from shortness of breath, extreme fatigue, rapid weight loss, night sweats and high fever. The doctors thought he might be suffering from tuberculosis and, even though they found no evidence of bacterial infection, they treated him for tuberculosis just to be safe, to no avail. The sailor continued to weaken and he died shortly after in August 1959. His autopsy revealed evidence of two unusual infections, cytomegalovirus and Pneumocystis carinii pneumonia (PCP, later, when redetermined as P. jirovecii, renamed Pneumocystis pneumonia), very rare at the time but now commonly associated with AIDS patients. His case had puzzled his doctors, who preserved tissue samples from him and for years retained some interest in solving the mystery. Sir Robert Platt, then president of the Royal College of Physicians, wrote in the sailor's hospital chart that he wondered "if we are in for a new wave of virus disease now that the bacterial illnesses are so nearly conquered". It was only 31 years later, after the AIDS pandemic had become well-known and widespread, that they decided to perform HIV-tests on the preserved tissues of the sailor, which initially turned out a positive result. The case was reported in the July 7, 1990 issue of the British medical journal The Lancet; their claim was retracted in a letter in the January 20, 1996 issue where they admitted that the tissue sample was contaminated in the laboratory (Corbitt G, Bailey A, Williams G. HIV infection in Manchester, 1959 . Lancet 1990; ii: 51.)^[28][29]

1959: Congolese man

One of the earliest documented HIV-1 infections was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo).^[30] However, it is unknown whether this anonymous person ever developed AIDS and died of its complications. ^[31]

1959: Haitian clerk

Another early case was probably detected that same year, 1959, in a 48-year-old Haitian, who 30 years before had immigrated to the United States and at the time was working as a shipping clerk for a garment manufacturer in Manhattan. He developed similar symptoms to those just described for the British sailor, and died the same year, apparently of the same very rare kind of pneumonia. Many years later, Dr. Gordon R. Hennigar, who had performed this man's autopsy, was asked whether he thought his patient had died of AIDS; he replied "You bet" and added "It was so unusual at the time. Lord knows how many cases of AIDS have been autopsied that we didn't even know had AIDS. I think it's such a strong possibility that I've often thought about getting them to send me the tissue samples."^[32]

1969: Robert R.

In 1969, a 15-year-old African-American male known to medicine as Robert R. died at the St. Louis City Hospital from aggressive Kaposi's sarcoma. AIDS was suspected as early as 1984, and in 1987, researchers at Tulane University School of Medicine confirmed this, finding HIV-1 in his preserved blood and tissues. The doctors who worked on his case at the time suspected he was a prostitute, though the patient did not discuss his sexual history with them in detail. ^{[33] [34] [35] [36] [37]}

1969: Arvid Noe

In 1976, a Norwegian sailor named Arvid Noe, his wife, and his nine-year-old daughter died of AIDS. The sailor had first presented symptoms in 1969, four years after he had spent time in ports along the West African coastline. Tissue samples from the sailor and his wife were tested in 1988 and found to contain the HIV-1 virus (Group O).^{[38][39] [40]}

1977: Dr. Grethe Rask

The next documented western death from AIDS was that of Dr. Grethe Rask in 1977. Rask, a Danish surgeon, had worked in the Congo in the early 1970s.

Gradual spread

A 2007 genetic study suggests that the HIV strains present in the early 1980s arrived in the United States from Haiti in the late sixties or early seventies. It is believed to have arrived in Haiti from central Africa, possibly through professional contacts with the newly independent Congo.^[41]

The disease has an incubation period of several years, and with a small incidence, was not noticed at first. Author Randy Shilts mentioned^{[citation needed]} that what was later called AIDS became evident in the gay community in the Fire Island, New York area in the four years after the 1976 US Bicentennial celebrations. The infection tended to double in numbers about every nine to ten months.

In the United States and Africa, HIV was at first mostly found only in residents of large cities. The infection is now more widespread in rural areas, and has appeared in regions such as China and India, where it was previously not evident.

1981-2: From GRID to AIDS

The AIDS epidemic officially began on June 5, 1981, when the U.S. Centers for Disease Control and Prevention in its Morbidity and Mortality Weekly Report newsletter reported unusual clusters of Pneumocystis pneumonia (PCP) caused by a form of Pneumocystis carinii (now recognized as a distinct species Pneumocystis jirovecii) in five homosexual men in Los Angeles.^[42]

Over the next 18 months, more PCP clusters were discovered among otherwise healthy men in cities throughout the country, along with other opportunistic diseases (such as Kaposi's sarcoma^[43] and persistent, generalized lymphadenopathy ^[44]), common in immunosuppressed patients.

In June 1982, a report of a group of cases amongst gay men in Southern California suggested that a sexually transmitted infectious agent might be the etiological agent,^[45] and the syndrome was initially termed "GRID", or Gay-Related Immune Deficiency.^[46]

Health authorities soon realized that nearly half of the people identified with the syndrome were not homosexual men. The same opportunistic infections were also reported among hemophiliacs,^[47] heterosexual intravenous drug users, and Haitian immigrants.^[48]

By August 1982, the disease was being referred to by its new CDC-coined name: Acquired Immune Deficiency Syndrome (AIDS). ^[49] It got these names in other languages:

• Afrikaans: VIGS (Verworwe Immuniteits Gebrek Sindroom)
• Portuguese: SIDA (Síndrome da Imunodeficiência Adquirida)
• French: SIDA: (Syndrome d'Immuno-Déficience Acquise)
• Spanish: SIDA: (Síndrome de Inmunodeficiencia Adquirida).^[50]
• Russian: SPID: (Синдром приобретённого иммунного дефицита (also иммунодефицита))
• Irish Gaelic: SEIF (Siondróm Easpa Imdhíonachta Faighte)

Genetic Studies

A 2007 study published in the Proceedings of the National Academy of Sciences by Michael Worobey and Dr. Arthur Pitchenik claimed that, based on the results of genetic analysis, HIV probably moved from Africa to Haiti and then entered the United States around 1969. ^[51]

Identification of the virus

May 1983: LAV

In May 1983, doctors from Dr. Luc Montagnier's team at the Pasteur Institute in France, reported that they had isolated a new retrovirus from lymphoid ganglions that they believed was the cause of AIDS. ^[52] The virus was later named lymphadenopathy-associated virus (LAV) and a sample was sent to the U.S. Centers for Disease Control, which was later passed to the National Cancer Institute (NCI).^{[53] [54]}

May 1984: HTLV-III

In May 1984 a team led by Robert Gallo of the United States confirmed the discovery of the virus, but they renamed it human T lymphotropic virus type III (HTLV-III).^{[55] [56]} The dual discovery led to considerable scientific disagreement, and it was not until President Mitterrand of France and President Reagan of the USA met that the major issues were resolved.

Jan 1985: both found to be the same

In January 1985 a number of more detailed reports were published concerning LAV and HTLV-III, and by March it was clear that the viruses were the same, were from the same source, and were the etiological agent of AIDS ^{[57] [58]}

May 1986: the name HIV

In May 1986, the International Committee on Taxonomy of Viruses ruled that both names should be dropped and a new name, HIV (Human Immunodeficiency Virus), be used. ^[59]

See also

• CCR5-Δ32

• AIDS Conspiracy Theories

Notes