TLR9/MyD88信号通路在HIV-1不易感中的作用及机制研究

项目名称： TLR9/MyD88信号通路在HIV-1不易感中的作用及机制研究

项目编号： No.81460511

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蒋俊俊

作者单位： 广西医科大学

项目金额： 50万元

中文摘要： HIV高暴露持续血清阴性者（HEPS）的HIV不易感机理尚未清楚。研究表明HIV抑制因子MIP-1α/β在HEPS中高表达，MX1/2可抑制HIV的感染和复制。我们前期发现TLR9、MIP-1α/β、MX1在HIV感染者中表达下降。TLR9通路可识别HIV感染，并可诱导产生MIP-1α/β和MX1/2，与三者都有直接关系。据此推测：TLR9/MyD88通路可上调MIP-1α/β、MX1/2的表达，阻止HIV在体内感染复制，从而在HEPS的HIV-1不易感中起关键作用。本项目利用HEPS人群调查和病毒-细胞系统研究，在体外激活或封闭TLR9通路，通过RT-PCR、WB等方法检测该通路关键因子的表达，分析其与HIV不易感的关系。本研究首次从免疫通路切入，体内外结合，从正反两面探讨TLR9/MyD88通路对HIV不易感的影响作用和机制，为揭示HEPS人群HIV不易感机理奠定基础。

中文关键词： 艾滋病；高暴露持续血清阴性；HIV-1不易感；TLR9/MyD88信号通路

英文摘要： So far the mechanism(s) of insusceptibility to HIV infection in HIV highly exposed persistently seronegative (HEPS) individuals has not been clearly understood. Previous studies have shown that the expression of two types of HIV inhibitor: MIP-1α/β is elevated in (HEPS) individuals. MIP-1α/β are the competitive ligands binging to CCR5 that is the receptor of HIV, while MX1/2 have the avility to inhibit the HIV infection and replication. Our preliminary data indicated that the expression of TLR9, MIP-1α/β, and MX1 decreased in HIV-1-infected individuals. It is well known that TLR9 recognizes HIV infection and activation of TLR9 pathway leads to production of MIP-1α/β and MX1/2. TLR9 has a direct relationship with all three factors. Thus, we hypothesize: TLR9/MyD88 signaling pathway plays a key role in HIV-1 insusceptibility through up-regulation of MIP-1α/β and MX1/2 expression, which can control HIV infection/replication in host cells. To verify our hypothesis, we will utilize HEPS population investigation and in vitro studies to detect the the expression of key factors in TLR9 pathway under the conditions of in vitro activating or blocking TLR9 pathway, thus illuminate the association of these factors with insusceptibility to HIV infection. This study, for the first time, explore the mechanism of HIV insusceptiblily from a new perspective- innate TLR9 signaling pathway. We expect this study will reveal the role of TLR9/MyD88 signaling pathway in HIV-1 insusceptibility. Our study, if successful, will lay the foundation for revealing the mechanism of HEPS and provide new strategy for HIV clinical treatment.

英文关键词： HIV/AIDS;Highly exposed and persistently seronegative;HIV insusceptibilty;TLR9/MyD88 signal pathway