BioWorld International Correspondent

LONDON - If the origins of the human immunodeficiency virus lie with the simian immunodeficiency virus (SIV) that infects chimpanzees, as scientists have recently concluded, that begs the question of where the chimpanzee SIV came from.

Now a team of scientists in the UK, U.S. and France has shown that the chimpanzee SIV, known as SIVcpz, is probably a hybrid of the ancestors of two recently characterized SIVs, one from the red-capped mangabey (SIVrcm) and the other from the greater spot-nosed monkey (SIVgsn).

Paul Sharp, professor of genetics at the University of Nottingham in the UK, told BioWorld International that although other researchers realized that the genetic sequence of both SIVs bore partial similarity to SIVcpz, they had assumed that the monkey viruses were each hybrids of the chimpanzee virus with other SIVs.

"We have now carried out a new type of analysis," he said, "which makes it suddenly clear that the chimpanzee virus is a hybrid of these two monkey viruses."

Sharp and his colleagues report their finding in the June 13, 2003, issue of Science, in a paper titled "Hybrid Origin of SIV in Chimpanzees."

The team analyzed the sequences of the viral genomes to find out which parts of the genome were more closely related to each. They found that one side of the genome of SIVcpz was closely related to SIVrcm, and that the other side was closely related to SIVgsn.

Sharp, who collaborates with Beatrice Hahn and her group at the University of Alabama at Birmingham said the finding would imply that chimpanzees must have become infected with both of the monkey viruses, which must have spread successfully in chimpanzees. He said, "Once an animal is infected by two divergent strains of a virus, those two viruses can recombine to form a hybrid virus."

Sharp added that out of about 10 chimpanzee SIVs that had been characterized, all are of the hybrid form. The group's earlier work has already shown that SIVcpz had been transmitted to humans on three separate occasions, because HIV-1 strains cluster into three separate groups on the viral evolutionary tree, with strains of SIVcpz scattered between them.

The work highlights some important differences and similarities between chimpanzees and humans. Sharp said: "The big difference is that, in chimpanzees as in naturally infected monkey species, SIV is not known to cause any disease symptoms. Since chimpanzees and humans are so similar genetically, we need to study chimpanzees more carefully to find out why this is."

It also appears that both chimpanzees and humans became infected with their respective viruses in similar ways. "Humans picked up these viruses from chimpanzees, presumably by hunting them, and now we are saying that chimpanzees have picked up these viruses a couple of times from monkeys, by hunting and eating them," Sharp said.

One important implication, he said, is that it is not a good idea for humans to hunt and eat chimpanzees or, presumably, any other kind of monkey that could be infected with an SIV. While chimpanzees probably picked up the virus by eating meat from infected monkeys, humans were more likely to have become infected during butchering the carcasses.

The group also is about to publish a paper in the Journal of Virology reporting their work surveying SIVcpz infection among the chimpanzees of Gombe National Park in Tanzania. They have devised tests that allow them to tell from urine samples whether an animal is infected and can extract viral RNA from fecal samples.

The study has shown that the prevalence of infection among these animals is "surprisingly low," Sharp said, at 10 percent to 15 percent. That level of infection contrasts to what is seen in most monkey species that have been studied in any detail, which often reaches 50 percent or more in adult animals.

"It's rather like what's seen in humans in parts of West Central Africa where the epidemic is at its oldest, where the prevalence of HIV is fairly stable at about 10 percent," Sharp said. "There is a parallel there, and it all says to us that we really need to study SIV infection of chimpanzees in the wild much more thoroughly and more widely. One very good reason for doing so would be that, because there are so many monkey species that have different SIVs, chimpanzees could have picked up some other strains that we don't know about yet. If those viruses have spread successfully in chimpanzees and are therefore adapted to infecting chimpanzees, they could presumably be a source of new HIVs by jumping into humans."