INTERFERON-GAMMA INDUCES RESISTANCE IN PRIMARY MONOCYTES AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

Treatment of monocytes with interferon-gamma 1 day before, or at the t ime of infection with human immunodeficiency virus type-1 (HIV-1) indu ced complete resistance in monocytes against HIV-1 infection. There wa s no evidence of viral RNA, proviral DNA, p24 antigen, or reverse tran scriptase activity through 2 weeks after inoculation. Ultrastructural examination of these cells showed no detectable virus particles. When interferon-gamma was added to monocytes 1 to 3 days post-infection, vi rus integration occurred, but the viral expression was either ablated (1 day postinfection) or significantly inhibited (3 days post-infectio n). Treatment of monocytes with interferon-gamma before or after infec tion with HIV-1 produced significantly higher levels of tumor necrosis factor-alpha and interleukin-8 than untreated or uninfected monocytes . These results suggest that altered regulation of cytokines may media te antiviral activity of interferon-gamma in monocytes. (C) 1994 Acade mic Press, Inc.