Interaction between herpesvirus entry mediator and HSV-2 glycoproteins mediates HIV-1 entry of HSV-2-infected epithelial cells
Interaction between herpesvirus entry mediator and HSV-2 glycoproteins mediates HIV-1 entry of HSV-2-infected epithelial cells
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疱疹病毒进入介质和 HSV-2 糖蛋白之间的相互作用介导 HIV-1 进入 HSV-2 感染的上皮细胞
DOI：
10.1099/jgv.0.000895
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发表时间：
2017-09-01
影响因子：
3.8
通讯作者：
Hu, Qinxue
中科院分区：
文献类型：
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作者：
Hu, Kai;He, Siyi;Hu, Qinxue
单纯疱疹病毒2型(HSV-2)通过不清楚的机制增加人类免疫缺陷病毒1型(HIV-1)的获得和传播。疱疹病毒进入介体(Hvem)是一种HSV-2进入受体，在HIV-1靶细胞(CD4(+)T细胞)上高表达，并可被掺入HIV-1病毒粒子中，而HSV-2糖蛋白可存在于感染细胞表面。由于hvem-gD与gB/Gh/gl的相互作用是HSV-2进入细胞所必需的，携带hvem的HIV-1(HIV-1/hvem)可能通过这种相互作用进入HSV-2感染的细胞。为了验证这一假设，我们首先证实了HIV-1病毒粒子和HSV-2感染细胞表面的糖蛋白上存在HVEM。进一步的研究表明，HIV-1/HVEM通过与HSV-2的相互作用，以HSV-2感染时间依赖的方式与HSV-2感染的细胞表面结合。HSV-2感染细胞的HIV-1/Hvem进入依赖于Hvem-gD相互作用和Gb/Gh/gl的存在，并被叠氮胸苷抑制。此外，外周血单个核细胞来源的HIV-1感染HSV-2感染的原代包皮上皮细胞，并被抗HSV-2/gD抗体抑制。综上所述，我们的结果表明，由CD4(+)T细胞产生的HIV-1携带HSV-2受体hvem，并能结合和进入HSV-2感染的上皮细胞，这取决于hvem-gD相互作用和Gb/Gh/gl的存在。我们的发现为HSV-2感染增强HIV-1粘膜传播提供了一个潜在的新机制，并可能为HIV-1的预防提供启示。
Herpes simplex virus type 2 (HSV-2) increases human immunodeficiency virus type 1 (HIV-1) acquisition and transmission via unclear mechanisms. Herpesvirus entry mediator (HVEM), an HSV-2 entry receptor, is highly expressed on HIV-1 target cells (CD4(+) T cells) and may be incorporated into HIV-1 virions, while HSV-2 glycoproteins can be present on the infected cell surface. Since HVEM-gD interaction together with gB/gH/gL is essential for HSV-2 entry, HVEM-bearing HIV-1 (HIV-1/HVEM) may enter HSV-2-infected cells through such interactions. To test this hypothesis, we first confirmed the presence of HVEM on HIV-1 virions and glycoproteins on the HSV-2-infected cell surface. Additional studies showed that HIV-1/HVEM bound to the HSV-2-infected cell surface in an HSV-2 infection-time-dependent manner via HVEM-gD interaction. HIV-1/HVEM entry of HSV-2-infected cells was dependent on HVEM-gD interaction and the presence of gB/gH/gL, and was inhibited by azidothymidine. Furthermore, peripheral blood mononuclear cell-derived HIV-1 infected HSV-2-infected primary foreskin epithelial cells and the infection was inhibited by anti-HVEM/gD antibodies. Together, our results indicate that HIV-1 produced from CD4(+) T cells bears HSV-2 receptor HVEM and can bind to and enter HSV-2-infected epithelial cells depending on HVEM-gD interaction and the presence of gB/gH/gL. Our findings provide a potential new mechanism underlying HSV-2 infection-enhanced HIV-1 mucosal transmission and may shed light on HIV-1 prevention.