Nottingham research sheds further light on the origins of HIV-1

Research led by Professor Paul Sharp at The University of Nottingham’s Institute of Genetics has shed further light on the origins of HIV-1, the virus that causes AIDS.

For more than 10 years, Professor Sharp has been collaborating with Professor Beatrice Hann, at the University of Alabama, on research aimed at clarifying the origins and evolution of AIDS viruses. In 1999, this team identified the origin of HIV-1 as being transmission of a virus (SIVcpz) from chimpanzees to humans, but a mystery remained concerning how chimpanzees acquired the virus in the first place. SIVs are a large family of viruses, carried by many species of monkeys in Africa, but chimpanzees are the only apes known to be naturally infected.

The latest results, published in the June 13 issue of Science, show that the chimpanzee virus is a hybrid of the SIVs naturally infecting two different species of monkeys, the red-capped mangabey and the greater spot-nosed monkey. It appears that, in the past, chimpanzees have picked up viruses from both monkeys, and then the hybrid formed from the two viruses. This hybrid virus spread through the chimpanzee species and was later transmitted to humans to become HIV-1. Chimpanzees commonly hunt and eat monkeys, and this most likely provided the route by which they acquired these monkey viruses. This is similar to the means by which humans probably first became infected, by butchering chimpanzees for ’’bushmeat’’.

There are other striking parallels between SIV infection of chimpanzees and HIV infection of humans. First, just as chimpanzees appear to have acquired SIVs from two different sources, humans are infected by two distinct AIDS viruses — in addition to HIV-1, there is HIV-2, which was acquired from sooty mangabeys in west Africa. Second, while monkeys may have been infected with SIVs for a very long time, chimpanzees have clearly acquired SIV more recently. Results from another part of this study, which will appear in the Journal of Virology in July, show that the prevalence of SIV infection in wild chimpanzees is much lower than in monkey species, and quite similar to the prevalence of HIV infection in those parts of west central Africa where the AIDS epidemic seems to have first emerged. The major difference between SIV infection of chimpanzees and HIV infection of humans is that chimpanzees are not known to develop any disease symptoms; given the very close genetic relationship between chimpanzees and humans, this prompts the question whether chimpanzees have co-evolved with their virus to reach this non-pathogenic association.

The implication of these results is that it will be important to broaden the study of natural SIV infection in wild chimpanzees. For example, it would be interesting to learn whether they have picked up SIVs from any other monkey species. Because of the similarity between chimpanzees and humans, any virus that successfully adapts to spreading among chimpanzees would be a candidate for a further jump to humans — a potential HIV-3.

It was previously known that the SIVs from red-capped mangabeys and greater spot-nosed monkeys are similar to the SIV from chimpanzees, within certain regions of their genomes. However, the evolutionary relationships among these viruses, and SIVs from other monkey species, have been difficult to disentangle. The researchers at The University of Nottingham, including research fellow Dr Liz Bailes, are evolutionary geneticists specialising in viral evolution, who developed a new approach to analyse these evolutionary relationships. This allowed the clear identification of the chimpanzee virus (SIVcpz) as being a hybrid of viruses ancestral to those from red-capped mangabeys (SIVrcm) and greater spot-nosed monkeys (SIVgsn): the left and right halves of the SIVcpz genome are closely related to SIVrcm and SIVgsn, respectively. The other co-authors are molecular virologists specialising in human and simian immunodeficiency viruses (HIVs and SIVs). These include groups at the University of Montpellier (France), and Tulane National Primate Center (USA), which have been responsible for isolating and characterising SIVs from various species of monkeys.