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 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 (IFN gamma) in HIV-1 replication in T cells. All five clones had similar phenotypes; and four clones constitutively produced IFN gamma and one clone did not. All five clones could be efficiently infected with HIV-1. HIV-1 infection of the IFN gamma-positive cells also upregulated IFN gamma mRNA production and IFN gamma secretion but not production 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 antibodies 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-positive T lymphocytes immortalized by HVS endogenous IFN gamma does not inhibit 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.
Saha
K
K
Molecular Virology Laboratory, St. Luke's-Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, New York 10019, USA.
Caruso
M
M
Volsky
D J
DJ
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D003588:Cytopathogenic Effect, Viral; D015497:HIV-1 / Q000502:physiology*; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009500:Neutralization Tests; D014779:Virus Replication
D007371:Interferon-gamma