HSV-2增加HIV-1感染的危险，但机制不明。我们在PBMC繁殖的HIV-1上检测到HSV-2入侵受体HVEM的存在（HIV-1/HVEM）；在HSV-2感染的细胞表面检测到病毒包膜糖蛋白的表达。我们推测，在共感染时，HIV-1可能可以通过HVEM与HSV-2包膜糖蛋白的相互作用而入侵非靶标细胞，这可能是HSV-2感染协助HIV-1建立感染的机制之一。初步研究发现，HSV-2感染的细胞能够吸附HIV-1/HVEM，且吸附能力与细胞表面病毒包膜糖蛋白水平相关；HIV-1/HVEM能够入侵表达HSV-2入侵必需糖蛋白的非靶标细胞。本申请拟在细胞系和原代细胞水平，从病毒吸附、入侵和入侵后行为三个层面，深入研究HSV-2包膜糖蛋白与受体HVEM相互作用介导的HIV-1感染非靶标细胞的能力。预期结果将有助于阐述HSV-2增强HIV-1感染的机制，并为HIV-1/HSV-2共感染的防治提供理论基础。

HSV-2 infection increases the risk of HIV-1 acquisition, but the underlying mechanisms remain unclear. We have previously detected the existence of HSV-2 entry receptor HVEM in PBMC propagated HIV-1 particles (termed HIV-1/HVEM) and the expression of viral glycoproteins on HSV-2 infected cell surface. We speculate that, under the condition of co-infection, HIV-1 with HSV-2 entry receptor(s) on the virus envelope may be able to infect HSV-2 infected cells (HIV-1 non-target cells) through interactions between HSV-2 entry receptor(s) and HSV-2 glycoproteins. This may be one of the potential mechanisms that HSV-2 enhances HIV-1 infection. Our pilot study showed that HSV-2 infected cells could be attached by HIV-1/HVEM in a HSV-2 glycoprotein cell surface expression dependent manner. In addition, HIV-1/HVEM could enter non-target cells expressing HSV-2 entry glycoproteins. The proposed study will focus on virus attachment, entry and the viral events post-infection. The anticipated outcomes would not only be important for understanding the possible mechanisms underlying HSV-2 mediated enhancement of HIV-1 infection, but also provide useful information for the prevention of HIV-1 and HSV-2 co-infection.