HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) INFECTION OF HERPESVIRUS SAIMIRI-IMMORTALIZED HUMAN CD4-POSITIVE T-LYMPHOBLASTOID-CELLS - EVIDENCE OF ENHANCED HIV-1 REPLICATION AND CYTOPATHIC EFFECTS CAUSED BY ENDOGENOUS INTERFERON-GAMMA

Herpesvirus saimiri (HVS) is a nonhuman primate gamma herpesvirus whic h can immortalize human T lymphocytes similar to Epstein-Barr virus im mortalization of B cells. The HVS-immortalized T cell lines can be clo ned and they remain functional, including susceptibility of CD4 expres sing T cells to infection with human immunodeficiency virus type 1 (HI V-1). In this report, we have used five such HVS-transformed CD4-posit ive T cell clones to reevaluate the role of endogenous interferon gamm a (IFN gamma) in HIV-1 replication in T cells. All five clones had sim ilar phenotypes; and four clones constitutively produced IFN gamma and one clone did not. All five crones could be efficiently infected with HIV-1. HIV-1 infection of the IFN gamma-positive cells also upregulat ed IFN gamma mRNA production and IFN gamma secretion but not productio n of IL-2 or IL-4. In contrast, infection of IFN gamma-negative cells did not induce IFN gamma, IL-2, or IL-4. Exposure to anti-IFN gamma an tibodies after HIV-1 infection significantly reduced virus production and inhibited virus-induced death of IFN gamma-positive cells but had no effect on IFN gamma-negative cells. We conclude that in CD4-positiv e T lymphocytes immortalized by HVS endogenous IFN gamma does not inhi bit HIV-1 but enhances HIV-1 replication and cytolysis. The potential augmenting effects of IFN gamma on HIV-1 replication in CD4-positive T cells recommend caution in a therapeutic use of this cytokine in AIDS . (C) 1997 Academic Press.