在与病毒长期共存过程中，宿主进化产生多种抗病毒限制因子抑制HIV感染过程的各个阶段，病毒也进化产生了相应的拮抗或逃逸机制。HIV感染宿主细胞始于其与细胞的结合及融合，主要由HIV包膜蛋白Env与细胞表面受体CD4及辅受体相互作用介导实现。本项目前期，我们克隆了一个新的能被I型干扰素诱导表达的宿主抗HIV因子。序列分析表明，该因子是一个G蛋白偶联受体，我们命名为GRAF。过表达GRAF显著抑制含有HIV Env的HIV假病毒NL4-3luc的感染；敲低GRAF促进假病毒的感染。但GRAF过表达或敲低对含有VSV-G包膜的假病毒的感染却没有影响。本项目拟在HIV-1天然宿主细胞中进一步明确GRAF的抗HIV-1功能，深入分析GRAF抑制HIV-1感染的分子机理。另一方面，我们将分析病毒是否编码拮抗GRAF的蛋白，并深入分析其拮抗机理。

The host has evolved multiple restriction factors that inhibit the replication of HIV at various steps of the viral life cycle, and the virus has also evolved mechanisms to counteract these restriction factors. HIV-1 infection of host cells begins with its binding and fusion with cell membrane. This process is mediated mainly by the interaction between HIV-1 envelope (Env) and the cell surface receptor CD4 and co-receptors. In our previous studies, we isolated a novel interferon-inducible host anti-HIV-1 factor. Sequence analysis revealed that the protein is a G protein-coupled receptor (GPCR), and we thus named it GRAF (GPCR-related antiviral protein). Overexpression of GRAF inhibited infection by HIV-1 Env pseudotyped NL4-3luc HIV-1 vector and downregulation of endogenous GRAF enhances infection by the HIV-1 vector. However, overexpression or downregulation of GRAF had little effect on the infection by VSV-G pseudotyped HIV-1 vector. In this project, we aim to understand the mechanism by which GRAF inhibits HIV-1 infection. In addition, we will analyze whether the virus encodes any antagonist against GRAF and explore the mechanism underlying the antagonism.