Kinetics of lymphocyte apoptosis in macaques infected with different simian immunodeficiency viruses or simian/human immunodeficiency hybrid viruses

Increased rates of T-cell apoptosis have been detected in human immunodefic iency virus (HIV)-infected individuals and in the simian immunodeficiency m odel (SIV) for AIDS research. We have infected macaques with virulent SIV o r SIV/HIV hybrid viruses (SHIV) of different pathogenic potentials to study the early kinetics of apoptosis in this model. Animals infected with SIV s howed an increased degree of apoptosis in their peripheral blood mononuclea r cells as early as 8 weeks after virus inoculation. Apoptotic cells were d etected in the CD4 and CD8 cell populations of infected animals. In contras t, apathogenic SHIV did not lead to increased lymphocyte apoptosis and mode rately pathogenic SHIV induced only transient apoptosis. T-cell death was t emporally linked to viral replication in vivo. Furthermore, lymphocyte apop tosis in infected macaques was associated with impaired proliferative respo nses of helper T-cells and with CD4 cell depletion. The monkey model descri bed here provides the opportunity for testing early therapeutic interventio ns to prevent virus-induced programmed cell death and the subsequent onset of AIDS. (C) 1999 Academic Press.