SERINC5（SER5）是新近发现的在不同物种间高度保守的宿主限制因子，能抑制多种逆转录病毒如HIV-1及MLV的感染性。然而，涉及到的详细机制以及SER5对活体内逆转录病毒复制能力及致病性的影响目前还不清楚。MLV是目前最典型、研究最透彻的逆转录病毒之一，也是目前揭示活体内逆转录病毒与宿主限制因子相互作用机制常用的病毒模型。我们前期结果发现SER5能抑制携带不同Env蛋白MLV的感染性，尤其是在glyco-Gag缺失的情况下。为进一步揭示SER5抗病毒活性的分子机制，本项目首先通过构建不同SER5突变体验证其抗病毒活性的功能区，然后利用SER5缺失细胞系揭示SER5限制MLV感染性的分子机制，最后利用构建的SER5基因敲除小鼠研究SER5对活体内MLV复制能力及致病性的影响。这些结果将为揭示SER5限制其他逆转录病毒感染性的机制提供理论基础，为抗逆转录病毒的治疗提供可借鉴的科学依据。

SERINC5 (SER5), highly conserved among different species, is a newly identified host restriction factor against different retroviruses including HIV-1 and MLV. However, when it comes to the more detailed molecular mechanisms and how such proteins influence the infectivity of retroviruses in vivo, many questions remain to be answered. MLV has been considered as a representative virus model to reveal the molecular interactions between the host restriction factors and the retroviruses. In our previous work, we found that SER5 could restrict the infectivity of distinct MLVs in different extent, especially in the absence of glyco-Gag. To designate the antiviral activity of SER5 in vitro, we determined to exploit different MLVs and truncated forms of SER5 to precisely locate the critical domains or amino acid sites of antiviral activity in SER5. Furthermore, the in-depth mechanisms regarding co-factors identification or host cellular pathways involvement would be investigated in terms of wild type and SER5 knock-out cell lines. However, considering the somewhat non-consistent situations existing between in vitro and vivo researches, we decided to employ SER5 knock-out mice to trace how SER5 executes its antiviral functions under the variable physiological environment in a long-term period. Thus, comprehensive and thorough knowledge concerning SER5 antiviral functions would be elucidated by the combined approaches. Outcomes of the study will provide a scientific basis for antiretroviral gene therapy.