tetano
Editor, Senior Moderator
Mol Cell
. 2021 Apr 13;S1097-2765(21)00313-0.
doi: 10.1016/j.molcel.2021.04.008. Online ahead of print.
Functional landscape of SARS-CoV-2 cellular restriction
Laura Martin-Sancho[SUP] 1 [/SUP], Mary K Lewinski[SUP] 2 [/SUP], Lars Pache[SUP] 1 [/SUP], Charlotte A Stoneham[SUP] 2 [/SUP], Xin Yin[SUP] 1 [/SUP], Mark E Becker[SUP] 3 [/SUP], Dexter Pratt[SUP] 4 [/SUP], Christopher Churas[SUP] 4 [/SUP], Sara B Rosenthal[SUP] 4 [/SUP], Sophie Liu[SUP] 4 [/SUP], Stuart Weston[SUP] 5 [/SUP], Paul D De Jesus[SUP] 1 [/SUP], Alan M O'Neill[SUP] 6 [/SUP], Anshu P Gounder[SUP] 1 [/SUP], Courtney Nguyen[SUP] 1 [/SUP], Yuan Pu[SUP] 1 [/SUP], Heather M Curry[SUP] 1 [/SUP], Aaron L Oom[SUP] 2 [/SUP], Lisa Miorin[SUP] 7 [/SUP], Ariel Rodriguez-Frandsen[SUP] 1 [/SUP], Fan Zheng[SUP] 4 [/SUP], Chunxiang Wu[SUP] 8 [/SUP], Yong Xiong[SUP] 8 [/SUP], Matthew Urbanowski[SUP] 9 [/SUP], Megan L Shaw[SUP] 10 [/SUP], Max W Chang[SUP] 4 [/SUP], Christopher Benner[SUP] 4 [/SUP], Thomas J Hope[SUP] 3 [/SUP], Matthew B Frieman[SUP] 5 [/SUP], Adolfo Garc?a-Sastre[SUP] 11 [/SUP], Trey Ideker[SUP] 12 [/SUP], Judd F Hultquist[SUP] 13 [/SUP], John Guatelli[SUP] 2 [/SUP], Sumit K Chanda[SUP] 14 [/SUP]
Affiliations
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.
Keywords: BST2; ISG; Orf7a; SARS-CoV-2; innate immunity; interferon; viral evasion.
. 2021 Apr 13;S1097-2765(21)00313-0.
doi: 10.1016/j.molcel.2021.04.008. Online ahead of print.
Functional landscape of SARS-CoV-2 cellular restriction
Laura Martin-Sancho[SUP] 1 [/SUP], Mary K Lewinski[SUP] 2 [/SUP], Lars Pache[SUP] 1 [/SUP], Charlotte A Stoneham[SUP] 2 [/SUP], Xin Yin[SUP] 1 [/SUP], Mark E Becker[SUP] 3 [/SUP], Dexter Pratt[SUP] 4 [/SUP], Christopher Churas[SUP] 4 [/SUP], Sara B Rosenthal[SUP] 4 [/SUP], Sophie Liu[SUP] 4 [/SUP], Stuart Weston[SUP] 5 [/SUP], Paul D De Jesus[SUP] 1 [/SUP], Alan M O'Neill[SUP] 6 [/SUP], Anshu P Gounder[SUP] 1 [/SUP], Courtney Nguyen[SUP] 1 [/SUP], Yuan Pu[SUP] 1 [/SUP], Heather M Curry[SUP] 1 [/SUP], Aaron L Oom[SUP] 2 [/SUP], Lisa Miorin[SUP] 7 [/SUP], Ariel Rodriguez-Frandsen[SUP] 1 [/SUP], Fan Zheng[SUP] 4 [/SUP], Chunxiang Wu[SUP] 8 [/SUP], Yong Xiong[SUP] 8 [/SUP], Matthew Urbanowski[SUP] 9 [/SUP], Megan L Shaw[SUP] 10 [/SUP], Max W Chang[SUP] 4 [/SUP], Christopher Benner[SUP] 4 [/SUP], Thomas J Hope[SUP] 3 [/SUP], Matthew B Frieman[SUP] 5 [/SUP], Adolfo Garc?a-Sastre[SUP] 11 [/SUP], Trey Ideker[SUP] 12 [/SUP], Judd F Hultquist[SUP] 13 [/SUP], John Guatelli[SUP] 2 [/SUP], Sumit K Chanda[SUP] 14 [/SUP]
Affiliations
- PMID: 33930332
- PMCID: PMC8043580
- DOI: 10.1016/j.molcel.2021.04.008
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.
Keywords: BST2; ISG; Orf7a; SARS-CoV-2; innate immunity; interferon; viral evasion.