학술논문
Functional landscape of SARS-CoV-2 cellular restriction
Document Type
article
Author
Martin-Sancho, Laura; Lewinski, Mary K; Pache, Lars; Stoneham, Charlotte A; Yin, Xin; Becker, Mark E; Pratt, Dexter; Churas, Christopher; Rosenthal, Sara B; Liu, Sophie; Weston, Stuart; De Jesus, Paul D; O'Neill, Alan M; Gounder, Anshu P; Nguyen, Courtney; Pu, Yuan; Curry, Heather M; Oom, Aaron L; Miorin, Lisa; Rodriguez-Frandsen, Ariel; Zheng, Fan; Wu, Chunxiang; Xiong, Yong; Urbanowski, Matthew; Shaw, Megan L; Chang, Max W; Benner, Christopher; Hope, Thomas J; Frieman, Matthew B; García-Sastre, Adolfo; Ideker, Trey; Hultquist, Judd F; Guatelli, John; Chanda, Sumit K
Source
Molecular Cell. 81(12)
Subject
Language
Abstract
A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.