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HIV Associated Cell Death by TNF Derived Peptides: Apoptosis Restricts Viral Transmission
Abstract
The human immunodeficiency virus (HIV) is still a global pandemic and despite successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV-induced death of lymphocytes and the effects on viral transmission. Flow cytometry analysis of lymphocytes from acute HIV infected patients, and HIV IIIB infected MT2 cells demonstrated both necrosis and apoptosis to be the major mechanisms of cell death in CD4+and CD4-/CD8- lymphocytes. Significantly, pro-apoptotic tumor necrosis factor (TNF) peptide was found to inhibit HIV-related cell death and reduced viral transmission. Whereas pro necrotic TNF peptide (P16) had little effect on HIV-related cell death and viral transmission. Understanding mechanisms by which cell death can be manipulated may provide additional drug targets to reduce the loss of CD4+ cells and the formation of a viral reservoir in HIV infection.