When it comes to battling the body's immune system, few viruses are as skilled as the one that causes AIDS. Yet despite years of scientific scrutiny, HIV has guarded its war strategies closely. Now new research, described today in the journal Nature, reveals one of the virus's secrets to success. According to the report, a protein dubbed Nef largely controls HIV's all-important ability to destroy the immune system cells dispatched to eliminate HIV-infected cells in the first place. This viral protein, the researchers say, protects infected host cells while destroying uninfected immune systems cells nearby.

Earlier research had shown that cells surrounding an HIV-infected cell die as a result of apoptosis, or programmed cell suicide, and scientists knew that Nef had a hand in starting that process. The new work, however, demonstrates that Nef uses that same trigger to protect its infected host cell, binding to and inhibiting an apoptosis protein called ASK1. "It's HIV going both ways, playing offense and defense," team member Warner C. Greene of the Gladstone Institute of Virology and Immunology observes. "It is a rather remarkable example of the cunning strategy the AIDS virus employs to help ensure its survival and spread."

The findings suggest that blocking the assembly of Nef and ASK1 could curtail HIV infection, and eventually lead to the death of the virus by not allowing it sufficient time to reproduce itself, Greene adds. (In fact, those rare HIV patients who happen to lack the nef gene progress to AIDS far more slowly than their nef-carrying counterparts.) Developing a drug that targets Nef, however, will first require that researchers discover a molecule to interrupt that assembly. "If we can win the battle at the single cell level," Greene notes, "then we will be in a better position to win the war in the millions of HIV-infected patients."