An international team of investigators claim to have discovered the missing link in the search for the origin of HIV-1 - the natural reservoir of the virus - which they have found to be in wild-living chimpanzees in southern Cameroon. The findings will be published in a future issue of Science magazine, and were made available online on May 25th in Sciencexpress.
The origin of HIV-1 has been the subject of speculation and ongoing research for many years. However, in 1999, American, Japanese and French researchers claimed to have discovered an indisputable link between a chimpanzee virus from central West Africa called SIVcpz (Simian Immunodeficiency Virus from chimpanzees) and HIV-1.
The species of chimpanzee this virus was found in is known as Pan troglodytes troglodytes (often shortened to P. t. troglodytes). SIVcpz was found to be 70-90% identical to HIV-1, and does not appear to cause illness in chimpanzees.
However, since SIVcpz was found in only a few P.t. troglodyte chimpanzees held in captivity, the possibility existed that another unidentified species could be the natural reservoir of both HIV-1 and SIVcpz.
In order to ascertain whether SIVcpz could be found in wild-living chimpanzees, investigators from the Universities of Nottingham (United Kingdom), Montpellier (France) and Alabama (United States) collaborated with the Project Prevention du Sida au Cameroun (PRESICA) in Cameroon, west-central Africa, in order to trace SIVcpz's molecular epidemiological links to HIV-1.
Wild-living chimpanzees are reclusive, highly endangered and live in remote jungle areas. Consequently, the most non-invasive method to identify SIVcpz is to analyse ape faecal samples collected from the forest floor. This is not a risk-free activity for the investigators, and previous attempts by others have led to loss of life.
A total of 446 faecal samples from ten sites were analysed, and SIVcpz antibodies and RNA was identified in 34 specimens, from 16 different P.t. troglodytes chimpanzees (seven males and nine females).
Prevalence rates were estimated for each of the ten sites, and the results (which ranged from 23-35% in three sites and 4-5% in two sites, to no prevalence in five sites) indicated a widespread but uneven prevalence of SIVcpz in wild-living chimpanzees.
The investigators then determined the genetic sequences of the chimpanzee viruses. Evolutionary analysis revealed an extremely close genetic relationship between some of the new chimpanzee virus samples and strains (groups M and N) of HIV-1.
Interestingly, the investigators found that chimpanzee communities from different geographic areas harboured distinct genetic variants of SIVcpz. Chimpanzees in south-east Cameroon were found to have viruses most similar to the form of HIV-1 that has spread throughout the world.
Paul M. Sharp, Professor of Genetics at The University of Nottingham, says that this is the culmination of more than a decade's work to find the source of HIV-1. "Particularly when you consider that HIV-1 probably originated more than 75 years ago, it is most unlikely that there are any viruses out there that will prove to be more closely related to the human virus," he says. "Thus, the initial jump of a virus from a chimpanzee to a human probably occurred in that region."
As well as possibly solving the mystery about the origin of HIV-1, the new findings also pave the way for future work exploring the natural history and behaviour of SIVcpz in its natural host, which may help scientists understand how to combat HIV-1 more effectively.
The authors of the study also postulate that, "given the extensive genetic diversity and phylogeographical clustering of SIVcpz now recognised, and the vast areas of west central Africa not yet sampled, it is quite possible that still other SIVcpz lineages exist that could pose risks for human infection and prove problematic for HIV diagnostics and vaccines."
Keele BF et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Sciencexpress, epub May 25th, 2006.