The mechanism by which HIV-1 kills CD4+ T lymphocytes remains largely unknown. A clear understanding of the death process occurring in infected cells may provide valuable insight to the viral component responsible for cytopathicity. This information, in turn, can aid in the design of preventative treatments against the rapid decline of CD4+ T cells that results in acquired immuno-deficiency syndrome (AIDS). Although numerous reports show evidence of apoptotic cell death among cultured T cell HIV-1 infections, typically only a minority of the infected dying cells exhibit characteristics of apoptosis. As such, we have studied HIV-1 induced cell death extensively by infecting several T cell lines and assessing the level of apoptosis using various biochemical and flow cytometric assays. Contrary to the prevailing view that apoptosis plays a prominent role in HIV-1-mediated T cell death, we found that Jurkat and H9 cells dying from HIV-1 infection fail to exhibit common hallmarks of apoptosis. Among the parameters investigated, Annexin V display, cleavage of caspase substrates, TUNEL positivity, and APO 2.7 display were detected at low to negligible levels. Furthermore, neither peptide caspase inhibitors nor molecular blockers of apoptosis effectively prevent cell death in HIV-1-infected cultures. These results suggest that the primary mode of HIV-1 cytopathicity is not via programmed cell death. Rather, cell death ensues most likely via a necrotic or lytic form of death independent of caspase activation.
Keywords: AEGIS, Caspases, Apoptosis, Antigens, CD4, T-Lymphocytes, HIV-1, Necrosis, In Situ Nick-End Labeling, Cell Death, Annexin V, HIV Infections, Receptors, Tumor Necrosis Factor, Human, deficiency, immunology, AIDS 000709
LbPeA7025
