Lewinski, Mary K
Stoneham, Charlotte A
Becker, Mark E
Rosenthal, Sara B
De Jesus, Paul D
O'Neill, Alan M
Gounder, Anshu P
Curry, Heather M
Oom, Aaron L
Shaw, Megan L
Chang, Max W
Hope, Thomas J
Frieman, Matthew B
Hultquist, Judd F
Chanda, Sumit K
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AbstractA 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.
Rights/TermsCopyright © 2021 Elsevier Inc. All rights reserved.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15589
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