Identification of the SHREK family of proteins as broad-spectrum host antiviral factors

Dabbagh, D.; He, S.; Hetrick, B.; Chilin, L.; Andalibi, A.; Wu, Y.

doi:10.1101/2021.02.02.429469

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bioRxiv · 10.1101/2021.02.02.429469

Identification of the SHREK family of proteins as broad-spectrum host antiviral factors

Dabbagh, D.·He, S.·Hetrick, B.·Chilin, L.·Andalibi, A.·Wu, Y.

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Abstract

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.

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Dabbagh, D., He, S., Hetrick, B., Chilin, L., Andalibi, A., Wu, Y.. 2021-02-03. Identification of the SHREK family of proteins as broad-spectrum host antiviral factors. https://doi.org/10.1101/2021.02.02.429469

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