Saha K, Caruso M, Volsky D J
Molecular Virology Laboratory, St. Luke's-Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, New York 10019, USA.
Virology. 1997 Apr 28;231(1):1-9. doi: 10.1006/viro.1997.8485.
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.
赛米利疱疹病毒（HVS）是一种非人类灵长类γ疱疹病毒，它能使人类T淋巴细胞永生化，类似于爱泼斯坦-巴尔病毒使B细胞永生化。HVS永生化的T细胞系可以被克隆，并且它们仍保持功能，包括表达CD4的T细胞对1型人类免疫缺陷病毒（HIV-1）感染的易感性。在本报告中，我们使用了五个这样的经HVS转化的CD4阳性T细胞克隆，以重新评估内源性干扰素γ（IFNγ）在HIV-1在T细胞中复制的作用。所有五个克隆都有相似的表型；四个克隆组成性地产生IFNγ，一个克隆不产生。所有五个克隆都能被HIV-1有效感染。IFNγ阳性细胞感染HIV-1也会上调IFNγmRNA的产生和IFNγ的分泌，但不会上调IL-2或IL-4的产生。相比之下，IFNγ阴性细胞的感染不会诱导IFNγ、IL-2或IL-4。HIV-1感染后暴露于抗IFNγ抗体显著降低了病毒产生，并抑制了IFNγ阳性细胞的病毒诱导死亡，但对IFNγ阴性细胞没有影响。我们得出结论，在由HVS永生化的CD4阳性T淋巴细胞中，内源性IFNγ不抑制HIV-1，而是增强HIV-1的复制和细胞溶解。IFNγ对CD4阳性T细胞中HIV-1复制的潜在增强作用建议在治疗艾滋病时谨慎使用这种细胞因子。
