HSV-2感染者被HIV-1感染的风险增加。HSV-2黏膜感染后招募HIV-1靶细胞到达感染局部可能是其促进HIV-1共感染的因素之一。我们曾发现HSV-2阳性患者的宫颈黏膜液中CXCL9含量增加，并发现HSV-2感染人宫颈上皮细胞后诱导表达CXCL9，且分泌的CXCL9在体外有趋化CD4+ T细胞迁移的活性，但是否在HIV-1黏膜共感染中发挥作用并不清楚。本项目拟在分子和人黏膜上皮细胞水平阐明起调控作用的病毒元件及其诱导CXCR3配体CXCL9、CXCL10和CXCL11表达的分子机制；在小鼠模型上评价HSV-2诱导的各CXCR3配体在招募CD4+ T细胞至宫颈组织的作用；利用极化的人黏膜组织模型探讨HSV-2诱导各CXCR3配体的表达及其对CD4+ T细胞分布和HIV-1共感染的影响。研究结果不仅有助于阐明HSV-2促进HIV-1共感染的分子机制，且可为HIV-1的预防提供新思路。

HSV-2 infection increases the risk of HIV-1 acquisition. Recruitment of HIV-1 target cells to infection areas after HSV-2 infection may be one of the mechanisms that account for increased HIV-1 sexual transmission. We previously demonstrated that the expression of a CXCR3 ligand CXCL9 is augmented in the cervical mucus of HSV-2–positive women. Furthermore, we showed that HSV-2 infection of human cervical epithelial cells induced the expression of CXCL9 and that the upregulated CXCL9 enhanced the migration of CD4+ T cells, the main target cells of HIV-1. However, the significance of HSV-2 induced CXCL9 in HIV-1 mucosal co-infection remains unknown. In this proposed study, we intend to investigate HSV-2 component(s) that regulates the expression of CXCR3 ligands CXCL9, CXCL10 and CXCL11 as well as the mechanisms of action at molecular and cellular levels. We will evaluate the roles of CXCR3 ligands in recruiting CD4+ T cell to cervical tissues of HSV-2 infected mice. Using a polarized human mucosal explant model, we will further address the influence of HSV-2 induced CXCR3 ligand expression on CD4+ T cell distribution and HIV-1 co-infection. The research outcomes would not only be important for understanding HSV-2 enhanced HIV-1 infection, but also provide information for the design of potential anti-HIV prevention strategy.