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-γ

Abstract

Herpesvirus saimiri (HVS) is a nonhuman primate gamma herpesvirus which can immortalize human T lymphocytes similar to Epstein-Barr virus immortalization of B cells. The HVS-immortalized T cell lines can be cloned and they remain functional, including susceptibility of CD4 expressing T cells to infection with human immunodeficiency virus type 1 (HIV-1). In this report, we have used five such HVS-transformed CD4-positive T cell clones to reevaluate the role of endogenous interferon gamma (IFNγ) in HIV-1 replication in T cells. All five clones had similar phenotypes; and four clones constitutively produced IFNγ and one clone did not. All five clones could be efficiently infected with HIV-1. HIV-1 infection of the IFNγ-positive cells also upregulated IFNγ mRNA production and IFNγ secretion but not production of IL-2 or IL-4. In contrast, infection of IFNγ-negative cells did not induce IFNγ, IL-2, or IL-4. Exposure to anti-IFNγ antibodies after HIV-1 infection significantly reduced virus production and inhibited virus-induced death of IFNγ-positive cells but had no effect on IFNγ-negative cells. We conclude that in CD4-positive T lymphocytes immortalized by HVS endogenous IFNγ does not inhibit HIV-1 but enhances HIV-1 replication and cytolysis. The potential augmenting effects of IFNγ on HIV-1 replication in CD4-positive T cells recommend caution in a therapeutic use of this cytokine in AIDS.