A new laboratory-made virus may provide AIDS researchers with the best animal model yet to study how HIV causes disease and how to thwart it with drugs, vaccines, and other interventions.
In the early days, AIDS researchers used chimpanzees to study HIV-1, the main driver of the human AIDS epidemic. But they soon realized that the virus does not cause disease in our closest genetic relatives, and the endangered animals also were in short supply and extremely expensive to work with. So researchers went down a step down on the primate ladder to monkeys--which had their own plusses and minuses as models. HIV-1 cannot copy itself in monkey cells, but SIV, its simian cousin, both replicates well in rhesus macaques and causes an AIDS-like disease. In order to make SIV closer to HIV-1, several labs later engineered hybrids called SHIVs-- SIVs that contain pieces of HIV.
Now, a team led Paul Bieniasz and Theodora Hatziioannou from the Aaron Diamond AIDS Research Center in New York City has moved one step closer to the real McCoy. "We've taught HIV-1 how to grow in monkey cells," says Bieniasz, a virologist who worked on the project for 2 years. "Bieniasz is going to put me out of business," jokes Ronald Desrosiers, who heads the New England Regional Primate Research center and helped pioneer the SIV model.
As Bieniasz and coworkers report in the 6 October Science, they took advantage of recent discoveries that two cellular mechanisms in rhesus macaque cells block HIV-1 replication. So the researchers took the small genetic sequences that allow SIV to dodge those blocks and stitched them into HIV-1. The new virus easily copied itself in monkey cells--at least in test tube experiments. Desrosiers says they "have done a beautiful job in working out a minimum of genetic changes to HIV-1 that allow robust replication." Nathaniel Landau of the Salk Institute for Biological Studies in San Diego, California, says he has tried to create the same viral hybrid with no luck. "It is an obvious idea, but getting it to work is very difficult," he adds.
Bieniasz's team has infected monkeys with the virus, dubbed simian tropic HIV-1, or stHIV-1, but he says it's too early to tell whether this will work as a new animal model. Regardless of whether this particular stHIV-1 proves its worth in monkeys, the study offers the first concrete evidence that a viral hybrid remarkably similar to HIV can replicate in monkey cells. "I know other investigators are hot on the trail, and we can expect further advancements in the not-too-distant future," says Desrosiers.