HIGH-LEVELS OF HIV-1 REPLICATION SHOW A CLEAR CORRELATION WITH DOWN-MODULATION OF BCL-2 PROTEIN IN PERIPHERAL-BLOOD LYMPHOCYTES OF HIV-1-SEROPOSITIVE SUBJECTS

Peripheral blood lymphocytes (PBLs) from 51 HIV-1-seropositive subject s with different levels of HIV-1 replication and 20 healthy blood dono rs were examined for the expression of the antiapoptotic Bcl-2 protein . All the plasma samples from HIV-1 patients were characterized for th e presence of HIV-1 p24 and HIV RNA viral load. Bcl-2 protein expressi on in fresh peripheral blood lymphocytes was studied by different test s, including Western blot and indirect immunofluorescence techniques. Direct immunofluorescence staining, revealed by flow cytometry, was ap plied to quantify the number of specific anti-Bcl-2 antibody epitope b inding sites, thus extrapolating the relative number of Bcl-2 into the cells. The results indicate that the expression of Bcl-2 protein is s ignificantly lower in peripheral blood lymphocytes of HIV-1-seropositi ve patients showing high levels of viral replication, detected by mean s of HIV-1 p24 and RNA viral load, with respect to HIV-1 patients with low levels of virus replication and healthy blood donors. The clear-c ut inverse correlation between viral replication and Bcl-2 expression reinforces the view that HIV-l-mediated apoptosis probably represents a key mechanism in AIDS pathogenesis. J. Med. Virol. 56:66-73, 1998. ( C) 1998 Wiley-Liss, Inc.