Origins Of HIV

So many questions have been posted since the discovery of the Human Immunodeficiency Virus but the most compelling has been that of its origins. Is it a new virus or an old virus that had lied dormant but going through mutations?

One way of tracing its origins was to look for similar viruses in non-human primates. Monkeys and apes were the most notable targets since they are known to be infected by some other important viruses that are known to infect man e.g. yellow fever virus.

In 1984 Max Essex et al examined large numbers of primates by serologically testing for cross-reactive epitopes in their sera. They found thus a monkey virus related to HIV in blood samples of the Asian macaques (macaca mulatta) housed at New England primate centre. At the same time captive macaques were reported to be developing AIDS-like symptoms, the virus was isolated and named SIV (simian immunodeficiency virus). It was clearly related to HIV; it infected the same CD4 subset of lymphocytes and reacted with antibodies produced by AIDS patients. The biochemical properties of SIV were similar to those of HIV.

Further studies have shown that SIV and HIV are 50% related at nucleotide level and that the organisation of structural and regulatory genes except that SIV has vpx gene which is not found in HIV and equally HIV has vpu gene not found in SIV. Like in humans with HIV, SIV infected monkeys showed decreased T4-cell count with evident immunosuppression and subsequent death to opportunistic infection.

What shocked researchers was that wild Asian macaques did not have any evidence of prior exposure to SIV or any HIV-like agent, thus infection had been limited to a small group of captive monkeys. This suggested that SIV did not naturally infect Asian monkeys in the wild.

In the same year blood samples from representative African primates, including wild caught chimpanzees (pan troglodytes); African green monkeys (cercopithecus aethiopis) and baboons (papio spp) were analysed. No evidence of SIV was found in chimpanzees or baboons but 50% of the African green monkeys did show evidence of SIV infection. Subsequent analysis of samples from other African Green monkeys has shown that 30-70% have SIV infection.

What puzzled investigators was why SIV does not seem to cause any disease or harm to AG monkeys yet wrecked havoc to Asian monkeys. This observation has also been made in that chimpanzees are the only animals that can be experimentally infected with HIV isolated from AIDS patients, yet the virus does not seem to cause any lethal disease in chimpanzees as it does in man.

Clearly SIV is the closest relative of the Human Immunodeficiency Virus, however the 50% relationship at nucleotide sequence level could not make it the immediate precursor of HIV, thus probably there were other intermediate viruses. In 1985 there was evidence in Senegal of such a virus.

It was found that about 10% of prostitutes there had antibodies that reacted with both HIV and SIV. Surprisingly the antibodies reacted much better with SIV than HIV particularly the external envelop glycoproteins. HIV-positive sera from US and central Africa did not react very well with the SIV envelope antigens. This virus was then called HIV-2, nevertheless studies have shown that people with HIV-2 have antibodies that are entirely reactive with SIV antigens. Genetic studies have shown that their nucleotide sequences are closely related too suggesting that these viruses share evolutionary roots.

Essex’s study showed that HIV-2 was endemic in West Africa. Isolation of HIV-2 from patients referred to Europe for treatment suggested that HIV-2 could in fact cause AIDS. Seroepidemiological studies showed that HIV-2 was transmitted sexually. Prostitutes who tested HIV-2 positive in 1985 were subsequently followed and examined for any abnormal clinical symptoms. In contrast to prostitutes in other parts of Africa with HIV-1, they showed negligible rates of lymphadenopathy, AIDS-related complex or AIDS itself. Thus the virulence of HIV-1 was greater as compared to HIV-2.