云南省主要流行的7型庚型肝炎病毒对HIV-1的增殖抑制作用及其分子机制研究

庚型肝炎病毒（GBV-C）是一种单股正链RNA病毒，该病毒本身无致病性，但可抑制HIV增殖、提高机体免疫、延缓HIV患者疾病进程，被誉为"潜在的HIV治疗剂"。不同GBV-C基因型对HIV的抑制效应具有差异，且目前少有报道与GBV-C直接作用的靶蛋白。因此，深入探讨GBV-C抑制HIV的作用机理是一个函待解决的关键科学问题。本研究基于课题组新发现的云南主要流行株GBV-C 7型毒株，通过7型GBV-C临床分离株与HIV-1共感染细胞，初步确定该毒株对HIV-1具有明显增殖抑制作用，进而拟通过7型GBV-C编码的功能蛋白，利用蛋白互作研究体系，从病毒和宿主两个层面出发，确定出与7型GBV-C功能蛋白直接作用的HIV-1靶蛋白和宿主靶蛋白，结合靶蛋白的生物学功能研究7型GBV-C抑制HIV-1的机制。本项目将为全面了解GBV-C与HIV间作用机制提供直接证据，并为预防和治疗HIV奠定理论基础。

GB Virus C/Hepatitis G Virus (GBV-C/HGV) is a positive stranded RNA virus. GBV-C infection has not been associated with any disease. However, several studies found that persistent GBV-C infection inhibited the HIV proliferation, improved the immunity system and survival ability in HIV-positive individuals. In fact, GBV-C has been considered as a potential anti-HIV agent. The genotype diversity of GBV-C contributes to its inhibitory effect on HIV. In addition, Target protein that directly associated with GBV-C was rarely reported. Thus, it is critical to deeply investigate the mechanisms of the inhibitory effects of GBV-C on HIV. We used the new GBV-C genotype 7 virus in Yunnan to perform the current study. We found that the GBV-C genotype 7 virus had significant effect on the inhibition of HIV proliferation. Based on the preliminary results, we'll use the functional protein that the genotype 7 virus encoded and the effective system for detecting protein-protein interaction to screen and identify the target proteins of HIV-1 and the host. Furthermore, we'll study the mechanism of the GBV-C anti-HIV based on the biological function of the target proteins. Our study can help to provide direct evidences to better understand the functional mechanism between GBV-C and HIV, and may provide a new insight into HIV prevention and treatment.