The HIV-1 vpr Protein Acts as a Negative Regulator of Apoptosis in a Human Lymphoblastoid T Cell Line: Possible Implications for the Pathogenesis of AIDS

摘要: Although apoptosis is considered one of the major mechanisms CD4+ T cell depletion in HIV-infected patients, virus-infected cells somehow appear to be protected from apoptosis, which generally occurs bystander cells. Vpr an auxiliary HIV-1 protein, which, unlike other regulatory gene products, present at high copy number virus particles. We established stable transfectants Jurkat constitutively expressing low levels vpr. These clones exhibited cycle characteristics similar those control-transfected Treatment control with apoptotic stimuli (i.e., cycloheximide/tumor necrosis factor α (TNF-α), anti-Fas antibody, or serum starvation) resulted a massive death by apoptosis. In contrast, all vpr-expressing showed impressive protection independently inducer. Notably, vpr antisense phosphorothioate oligodeoxynucleotides render as susceptible induced cycloheximide and TNF-α clones. Moreover, constitutive expression upregulation bcl-2, oncogene endowed antiapoptotic activities, downmodulation bax, proapoptotic bcl-2 family. Altogether, these results suggest that endogenous protein can interfere physiological turnover lymphocytes early stages infection, thus facilitating HIV persistence and, subsequently, viral spread. This might explain why mostly uninfected AIDS patients.