The recent discovery of another HIV virus has prompted an early warning from primate researchers about the possibility of "mosaic" HIV epidemics, all raging at the same time. In the September issue of Nature Medicine, French researcher François Simon of the Hôpital Bichat in Paris and African colleagues at the Pasteur Institute in Cameroon reported discovering a highly virulent strain of HIV in a Cameroon woman distinct from existing strains of HIV-1. Further screening turned up another two people with the unique virus, dubbed "group N."

An analysis of group N's genetic structure shows that it probably did not descend from the two main human HIV viral groups (groups O and M). Instead, the group N virus has genes that place it at an equal distance on the evolutionary tree of retroviruses from group M and a chimpanzee virus called SIVcpz (the primate counterpart to HIV-1). Simon thinks group N virus infected humans via cross-species transmission-the jumping over of simian viruses into humans. If this likely scenario proves true, it raises the possibility that other SIV strains may cross into humans. And that can cause big trouble: if a vaccine is developed against current mutations of the virus, it might not work as well or even at all against a novel emerging strain.

"This is a very serious issue, and I don't think even my colleagues in the field have fully appreciated its significance," says Preston Marx, a leading primate researcher at Tulane University and the Aaron Diamond AIDS Research Center in New York City. In Marx's view, the discovery of group N may have grave public-health consequences: "There are several possibilities for how this virus got here," he says. "It could be an introduction of a new HIV strain that's adapted to humans but has infected very few people. Or it could be the emergence of a new virus that's going to replace existing strains. Right now, we don't know which is which. But that's a scary thing." After praising Simon's research, Marx adds: "It raises an awful lot of questions."

To understand why Marx and Simon are sounding the alarm, take a look at HIV's family tree. HIV retroviruses are divided into two types, HIV-1 and HIV-2, and both are examples of cross-species transmission. Up to now, HIV-1 was broken down into the two main groups, O and M; group M encompassed 10 divergent subtypes labeled A through J.

Each subtype is dominant in certain parts of the world. For example, subtype B is prevalent in the U.S. But since HIV mutates so quickly, it's spawning many "recombinant" viruses. One example is B/C, a strain that is spreading in southwest China and carries genes from its parent subtypes. At the 12th World AIDS Conference in Geneva, HIV researcher Jaap Goudsmit warned that recombinant mutant strains of HIV can be dangerous because they may be resistant to current HIV drugs.

HIV-2 causes a very slow immune disease in humans that resembles AIDS and is reportedly endemic in southern Africa and the Caribbean. People can carry this virus for years without getting sick, though they eventually do. Some people are co-infected with both human viruses. The SIV retroviruses are also endemic in many species of primates but usually don't cause disease, which makes them natural hosts for what are known as lentiviruses-slow-acting viruses. But when they cross the species barrier into a new host like humans, these viruses become pathogenic, causing illness.

Based on evolutionary studies, researchers think SIV has existed in sub-Saharan Africa for thousands of years, adapting to several species including the African green monkey and sooty mangabey. There are six closely linked strains of SIV. Chimpanzees carry a viral predecessor of HIV-1, while sooty mangabeys carry an ancestor of HIV-2. The newly identified group N is likely to have mutated through generations of chimpanzees before crossing the species barrier into humans to cause AIDS. Now the critical questions are how widespread this virus is among humans and whether the virus will get more virulent as it spreads.

Simon's discovery also raises other critical questions and challenges. Looking ahead, how many other SIV strains may have crossed the species barrier? Should we be mass screening for this new virus or increasing surveillance of the other SIV strains? What about the human recombinant viruses? How well are we tracking them? In Marx's opinion, more scientific information is needed about group N before we invest in a costly mass-screening program. "First we have to identify the exact mechanism of crossover for the virus," he says. He's currently fingering what are called accessory genes, which allows SIV to be transmitted to humans. Work by several groups suggests that accessory genes called Vpr and Vif in the sooty mangabey, for example, can function in human cells as well. Without these accessory genes, a primate virus can't be transmitted to a human, Marx believes.

Ongoing work by Simon's group and other teams aims to fill in the picture. At the University of Alabama at Birmingham, renowned virus hunter Beatrice Hahn is doing groundbreaking work on HIV-2. Together, Hahn and Marx have identified nine non-epidemic strains of HIV-2, labeled A through F; only A and B appear in humans. The duo is now heading to Gabon to study group N and its primate cousins.