HIV Defense Mechanism Uncovered

Discriminating. HIV blocks a defensive protein in humans but not mice.

The AIDS virus dodges the immune system's barrage of ammunition. Now researchers have uncovered one of its tricks: HIV disables a host protein that otherwise would break the virus into pieces. But the virus can't stop similar proteins in mice. The finding, published in the 11 July issue of Cell, provides a new clue about why HIV infects only humans and may someday lead to better animal models of AIDS.

Last year scientists discovered that a protein made by HIV, called Vif, protects the virus from host attack. But they weren't sure how Vif pulled off this feat. Now AIDS researcher Nathaniel Landau of the Salk Institute for Biological Studies in San Diego, California, and colleagues report that Vif locks down a human protein called APOBEC3G. In the absence of Vif, APOBEC3G slides into the virus and pulls out bits of its DNA, inactivating it. Vif thus protects HIV against extermination in human cells.

Curious how mice fight off HIV so easily, Landau's group checked to see if the rodents have their own version of the APOBEC3G gene. They did, but the mouse protein, the researchers found, is unrecognizable to HIV's defense system. It bypassed the Vif blockade, wiggled into the virus, and knocked it out of commission.

“It's a major breakthrough” to show that APOBEC3G plays a role in humans' unique susceptibility to HIV, says Jeremy Luban, a virologist at Columbia University. For scientists studying HIV drugs and vaccines, "it would be an enormous technical advantage" if this information could help create laboratory mice that can sustain HIV infection, he says. But Luban cautions that such a project is not likely to bear fruit immediately, as there are likely many other obstacles preventing HIV from infecting other species.

Related sites
Nathaniel Landau's lab Jeremy Luban's lab