Our findings indicate that although in acute infection Type I IFN may exert an important antiviral effect, during chronic HIV-1 infection, IFNα/β may contribute to the loss of CD4+ T cells and the failure of HIV-specific CD8+ T cells to control viral replication by upregulating Bak and sensitizing T cells to CD95/Fas-induced apoptosis. The gene discussed is CD8A; the disease is HIV-1 infection.