Cell receptors drop with HIV infection.

Cell receptors drop with HIV infection

Knowing why some immune cells in the body can harbor the AIDS-associated virus (HIV) and still survive could prove crucial in AIDS treatments. Hidden inside these cellular sanctuaries, the virus apparently lies in wait -- until unknown factors reactivate it and the immune cells are destroyed. On the basis if a new study using chronically infected T4 lymphocytes, scientists now say the appearance of HIV envelope material on the surface of these immune cells after infection actually makes them "cytolysis resistant," protected from virus-induced rupture during the latent period.

After inserting the HIV-envelope gene into T4 lymphocytes to create chronic infections in the cells, scientists at the University of Nebraska Medical Center in Omaha looked at the concentration of CD4 receptors on cell surfaces. These common T-lymphocyte molecules are in part responsible for interactions between a cell and another structure, whether other cells or foreign antigens. The researchers found that, as HIV-envelope structures appeared on T4-cell surfaces, the number of CD4 receptors on HIV-gene-containing cells dropped by about 60 percent, compares with that on unaltered cells. The CD4 receptors are thought to be important in binding HIV to cells during the infection process.

When mixed with HIV in the laboratory, the gene-containing cells were resistant to killing by the virus, whereas cells that had not been injected with the envelope gene prior to HIV exposure died. The treated cells also were resistant to repeated HIV exposure. According to the scientists, this phenomenon can occur with retroviruses other than HIV, including HTLV-1, recently linked to human leukemia and lymphoma. Because this loss of receptors may postpone the HIV-mediated death of T4 lymphocytes, which correlates with the appearance of AIDS symptoms, it has "important implications for both the pathogenesis of and treatment strategies for AIDS," the group writes in the May 6 CELL.

The authors also say they disagree with current scientific opinion that the rupture of infected cells may depend on the presence of syncytia -- giant cells formed when lymphocytes clump around an infected cell and their membranes fuse. After adding a chemical known to greatly enhance HIV replication, the scientists found the majority of chronically infected lymphocytes died within 96 hours. They say this effect occurred despite the absence of CD4 and syncytium formation .