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 (Ha-CoV-2) pseudovirus. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.
【저자키워드】 SARS-CoV-2, influenza A, HIV-1, CD34, MUC4, Ha-CoV-2, SHREK, PSGL-1, PODXL1, PODXL2, CD164, TMEM123, 【초록키워드】 viruses, Antiviral, Infection, Proteins, virus, P-selectin, MUC1, Protein, Characteristics, pseudovirus, glycoprotein, mucin, cellular, host innate immunity, target cells, Factor, domain, virion, surface protein, block, Host, Cell, Extracellular, virus, addition, restrict, subset, inhibiting, glycosylated, CD43, 【제목키워드】 family, identification, Factor,