HIV Subterfuge Revealed -- Virus Uses Devious Strategy To Undermine Immune System

The scientists found that even when HIV does not enter a cell, proteins in the outer envelope of the virus can bind to a molecule called CCR5 on the cell's surface and initiate a biochemical cascade that sends a signal to the cell's interior. This signalling process mayactivate the cell, making it more vulnerable to HIV infection. It alsomay cause cells to migrate to sites of HIV replication, thereby increasing their vulnerability to infection. If the cell is already infected with HIV, activation may boost its production of the virus.

Drew Weissman, M.D., Ph.D., formerly of the NIAID Laboratory of Immunoregulation (LIR) and now an assistant professor at the University of Pennsylvania; Ronald L. Rabin, M.D., of the NIAID Laboratory of Clinical Investigation; Anthony S. Fauci, M.D., NIAID director and LIR chief; and their colleagues report the new findings inthe Oct. 30, 1997 issue of the journal Nature.

"These new data add to our understanding of the complex ways HIV causes disease," says Dr. Fauci. "It is a truly formidable foe with many tricks up its sleeve." Adds Dr. Weissman, "Our findings suggest that HIV, even without infecting a cell, canprofoundly influence the disease process by activating cells andinfluencing their movement and aggregation."

HIV generally requires two receptors to enter a target cell: CD4, and either CCR5 or CXCR4, depending on the strain of virus. The strains of HIV most commonly seen early in HIV disease, known as macrophage-tropic (M-tropic) viruses, use CD4 and CCR5 for cellentry. Many strains of the simian immunodeficiency virus (SIV), acousin of HIV that infects non-human primates such as monkeys, also use these receptors for cellular entry.

As described in the Nature report, the researchers found that envelope proteins from four different M-tropic HIV strains and one M-tropic SIV strain induced a signal through CCR5 that caused cells to migrate in culture. In contrast, envelope proteins from other strains of the viruses, known as T-cell tropic (T-tropic) strains, did not causesignalling.

"HIV disease is characterized by persistent immune activation, and envelope protein-mediated signalling through CCR5 may contribute directly or indirectly to this heightened state of activation, with negative consequences for the HIV-infected person," Dr. Faucisays.

Not only are HIV replication an