HIV protein prepares virus' victims.

Once HIV infects a person, it risks falling victim to its own deadliness. The AIDS virus reproduces efficiently only inside immune cells that have been activated out of their natural resting state, yet it ultimately kills those cells. Moreover, very few immune cells in the body are normally in the activated state.

"This creates a problem for the virus. Very quickly, it will run out of suitable hosts," says Chiang J. Li of the Dana-Farber Cancer Institute in Boston.

Li and his colleagues may now have found how HIV resolves this apparent paradox The virus makes a protein that activates quiescent immune cells and transforms them into suitable hosts for replication, they report in the July 22 Proceedings of the National Academy of Sciences.

"HIV, being a very adaptive virus, has in its evolution been able to develop a way to help its own replication," notes Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The viral protein in question goes by the name of Tat. Scientists have long recognized its ability, when inside cells, to turn on viral and cellular genes. Now, Li's group has disclosed a novel extracellular role for the protein.

Cells infected with HIV typically secrete large amounts of Tat. Researchers have hypothesized that the secreted protein stimulates the proliferation of some cells, leading to AIDS-related cancers such as Kaposi's sarcoma.

Two years ago, Li and his colleagues reported that immune cells exposed to Tat sometimes commit suicide. As they examined their results more closely, however, the investigators realized that the majority of immune cells exposed to Tat simply became activated.

In the new research, Li's team shows that immune cells exposed to Tat display on their surface proteins that are characteristic of activated cells.

The investigators then established that the AIDS virus reproduces efficiently inside the Tat-activated cells. Moreover, antibodies that bind Tat prevent the protein from priming the immune cells for HIV reproduction, they report.

The researchers further discovered that the viral protein activates immune cells by binding to cell surface proteins called integrins, which then trigger a signaling cascade within the cell.

Li suggests that his group's research should encourage efforts to develop drugs or a vaccine that will block Tat's actions.

That may be easier said than done, says Fauci, noting that several drug companies have already pursued such Tat inhibitors vigorously and met with failure.

"It was clear that the virus has a number of ways to evade our attempts to interfere with Tat. So at least the first round of that fight was given up by the drug companies," says Fauci. Still, the work of Li's group may inspire those firms to tackle Tat once again, he adds.