干扰素诱导跨膜蛋白抑制SARS-CoV-2流行变异株感染侵入的分子机制研究

新型冠状病毒（SARS-CoV-2）流行变异株的广泛传播为疫情防控带来巨大挑战。当前研究多集中于监测流行变异株对现有疫苗的敏感性，而变异株的固有免疫尚缺少系统研究。干扰素诱导跨膜蛋白（IFITM）是近年发现的具有广谱抗病毒能力的重要固有免疫防御分子。申请人前期工作发现IFITM显著抑制包括B.1.1.7在内的多种新冠病毒流行变异株，并发现：流行变异株含有的D614G突变改变了病毒侵入途径。因此，申请人提出假说“流行变异株利用D614G突变改变了病毒感染侵入途径，进而影响IFITM对SARS-CoV-2及其变异株的限制作用”。本课题拟通过研究D614G介导的SARS-CoV-2侵入途径的改变以及IFITM亚细胞定位与IFITM抑制SARS-CoV-2侵入作用的内在关系，深入揭示IFITM调控SARS-CoV-2及其变异株感染侵入的分子机制，为控制病毒感染提供新的理论依据。

The widespread of SARS-CoV-2 epidemic variants have brought enormous challenge for epidemic prevention and control. Most of the current research is focusing on monitoring the sensitivity of variant strains to existing vaccines, while the innate immunity of the variant strains is still lacing in systematic research. Interferon-induced transmembrane protein (IFITM) is a recent discovered important defense molecule of innate immune induced by interferon. Our previous work found that IFITM significantly inhibited a variety of epidemic variants including B.1.1.7 (501Y.V1), and further suggested that the D614G mutation of the spike protein increased the inhibitory ability of IFITM. Thus we propose a hypothesis that D614G might affect the restriction effect of IFITM on SARS-CoV-2 and its variants by altering the viral entry route. We will investigate the different invasion pathway of SARS-CoV-2 and D614G mutant as well as the subcellular location of IFITM, so that further reveal the mechanism of invasion and entry pattern of SARS-CoV-2 and its variants regulated by IFITM, all of which will add new theoretical basis for the control of viral infection.