MADISON -- Scientists have shown for the first time, using a nonhuman primate model, that the AIDS virus avoids the body's strongest immune responses during the first few weeks of infection. The finding, which appears in the Sept. 21 issue of Nature, opens the door to new vaccine directions.
"We have discovered a potentially promising new approach to attack the AIDS virus," says David Watkins, professor of pathology and laboratory medicine at the University of Wisconsin-Madison.
"We have found that this early immune evasion allows the virus to sidestep a massive killer T cell response that occurs soon after infection," he added. "These results show that infected individuals do make immune responses that the virus cannot tolerate. The challenge will be to mimic these responses in an HIV vaccine."
Watkins, post-doctoral researcher Todd Allen and graduate student David O'Connor studied rhesus macaques infected with the monkey equivalent of HIV at the Wisconsin Regional Primate Research Center in Madison. Two weeks after infection and before the immune response fully developed, the virus remained unchanged from the stock used to infect the animals.
Shortly thereafter, the killer T-cell immune response that the researchers discovered began to combat the virus. Killer T cells are found throughout the body and are one of the immune system's most powerful weapons; they quickly and directly kill virally infected cells.
Four weeks after infection, the scientists could no longer isolate the original virus. Instead, a different virus predominated, one with changes in the region of the virus recognized by the immune response. They mapped this region to the small viral Tat protein, and showed that this Tat-specific killer T-cell response is the most potent early cellular immune response in these animals.
"The virus entirely escaped from the Tat-specific immune response within the first few weeks of infection," Watkins says. "The new virus was no long
Contact: David Watkins
University of Wisconsin-Madison