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Functional landscape of SARS-CoV-2 cellular restriction.
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.
  • Martin-Sancho L; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Lewinski MK; Department of Medicine, University of California San Diego, and the VA San Diego Healthcare System, San Diego, CA 92161, USA.
  • Pache L; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Stoneham CA; Department of Medicine, University of California San Diego, and the VA San Diego Healthcare System, San Diego, CA 92161, USA.
  • Yin X; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Becker ME; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Pratt D; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Churas C; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Rosenthal SB; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Liu S; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Weston S; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • De Jesus PD; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • O'Neill AM; Department of Dermatology, University of California San Diego, La Jolla, CA 92093, USA.
  • Gounder AP; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Nguyen C; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Pu Y; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Curry HM; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Oom AL; Department of Medicine, University of California San Diego, and the VA San Diego Healthcare System, San Diego, CA 92161, USA.
  • Miorin L; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA.
  • Rodriguez-Frandsen A; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Zheng F; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Wu C; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA.
  • Xiong Y; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA.
  • Urbanowski M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA.
  • Shaw ML; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; Department of Medical Biosciences, University of the Western Cape, Cape Town 7535, South Africa.
  • Chang MW; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Benner C; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Hope TJ; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Frieman MB; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine
  • Ideker T; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
  • Hultquist JF; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Guatelli J; Department of Medicine, University of California San Diego, and the VA San Diego Healthcare System, San Diego, CA 92161, USA.
  • Chanda SK; Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: schanda@sbpdiscovery.org.
Mol Cell ; 81(12): 2656-2668.e8, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1179919
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Interferon Type I / Antigens, CD / Interferon Regulatory Factors / Host-Pathogen Interactions / SARS-CoV-2 Type of study: Experimental Studies / Prognostic study Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: J.molcel.2021.04.008

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Interferon Type I / Antigens, CD / Interferon Regulatory Factors / Host-Pathogen Interactions / SARS-CoV-2 Type of study: Experimental Studies / Prognostic study Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: J.molcel.2021.04.008