HSV-2感染对黏膜组织中HIV-1受体表达及易感细胞分布的影响研究

性传播已成为全球HIV-1传播的主要途径。研究表明HSV-2感染能增加HIV-1性传播的几率。HSV-2增加HIV-1黏膜感染有多种可能但有待证实的机制：破坏黏膜屏障、增加HIV-1靶细胞数量、促使靶细胞在感染部位聚集、增加HIV-1受体表达等。围绕HIV-1建立黏膜感染这一重要科学问题，本项目拟在已取得的部分实验结果的基础上，利用建立的极化黏膜组织感染模型，研究HSV-2是如何通过改变黏膜组织中免疫细胞表面HIV-1受体表达水平、HIV-1易感细胞的分布情况，从而达到增加HIV-1的黏膜感染与传播，探讨HSV-2和HIV-1黏膜共感染的机制。研究结果不仅将为进一步揭示HSV-2与HIV-1黏膜协同感染和免疫逃逸机制建立实验系统，而且将为研发针对HSV-2和HIV-1的杀微生物剂和黏膜疫苗提供理论依据。

Sexual transmission is the leading mode of HIV-1 acquisition worldwide. HSV-2 infection has been shown to increase the risk of HIV-1 transmission. Several potential mechanisms underlying HSV-2 increased HIV-1 susceptibility have been proposed: damage of epithelial layer, increase of HIV-1 target cell number, recruitment of HIV-1 target cells to infection sites, and enhancement of the levels of HIV-1 receptors. To understand how HIV-1 establishes mucosal infection, this proposed study will be carried out by using a previously established polarized mucosal explant model of human mucosal tissue. We will address how HSV-2 infection impacts the expression level of HIV-1 receptors and the distribution of HIV-1 target cells in the mucosal tissue to increase HIV-1 infection, and explore the potential mechanisms of HSV-2 and HIV-1 co-infection. The outcomes of this study will not only establish an experimental model for investigating the mechanisms underlying HSV-2 and HIV-1 co-infection, but also provide key information for the development of topical microbicides and mucosal vaccines against HSV-2 and HIV-1 transmission.