Dabbagh Deemah, He Sijia, Hetrick Brian, Chilin Linda, Andalibi Ali, Wu Yuntao
bioRxiv. 2021 Feb 3:2021.02.02.429469. doi: 10.1101/2021.02.02.429469.
Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123), that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 virus-like particle. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.
黏蛋白和黏蛋白样分子是高度糖基化的高分子量细胞表面蛋白，具有半刚性且高度伸展的细胞外结构域。P-选择素糖蛋白配体-1（PSGL-1）是一种黏蛋白样糖蛋白，最近发现它通过病毒体掺入来限制HIV-1感染性，这种掺入在空间上阻碍病毒颗粒附着于靶细胞。在此，我们报告鉴定出一类抗病毒细胞蛋白，命名为病毒体灭活剂的表面铰链、刚性伸展杀手（SHREK）家族（PSGL-1、CD43、TIM-1、CD34、PODXL1、PODXL2、CD164、MUC1、MUC4和TMEM123），它们与PSGL-1具有相似的结构特征。我们证明SHREK蛋白通过抑制病毒颗粒附着于靶细胞来阻断HIV-1感染性。此外，我们证明SHREK蛋白是广谱宿主抗病毒因子，可阻断多种病毒如甲型流感病毒的感染。而且，我们证明一部分SHREK蛋白还能阻断杂交甲型病毒-SARS-CoV-2病毒样颗粒的感染性。这些结果表明，SHREK蛋白可能是宿主针对包膜病毒的固有免疫的一部分。
