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Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors

Cell host & microbe, 2021-02, Vol.29 (2), p.267-280.e5 [Peer Reviewed Journal]

2020 Elsevier Inc. ;Copyright © 2020 Elsevier Inc. All rights reserved. ;2020 Elsevier Inc. 2020 Elsevier Inc. ;ISSN: 1931-3128 ;EISSN: 1934-6069 ;DOI: 10.1016/j.chom.2020.12.009 ;PMID: 33357464

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Title:
Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors
Author: Hoffmann, H.-Heinrich ; Sánchez-Rivera, Francisco J. ; Schneider, William M. ; Luna, Joseph M. ; Soto-Feliciano, Yadira M. ; Ashbrook, Alison W. ; Le Pen, Jérémie ; Leal, Andrew A. ; Ricardo-Lax, Inna ; Michailidis, Eleftherios ; Hao, Yuan ; Stenzel, Ansgar F. ; Peace, Avery ; Zuber, Johannes ; Allis, C. David ; Lowe, Scott W. ; MacDonald, Margaret R. ; Poirier, John T. ; Rice, Charles M.
Subjects: coronavirus ; Coronavirus 229E, Human - genetics ; Coronavirus 229E, Human - metabolism ; Coronavirus NL63, Human - genetics ; Coronavirus NL63, Human - metabolism ; Coronavirus OC43, Human ; COVID-19 ; COVID-19 - virology ; CRISPR ; CRISPR-Cas Systems ; Genes, Viral ; HCoV ; HCoV-229E ; HCoV-NL63 ; HCoV-OC43 ; Host-Pathogen Interactions ; Humans ; Resource ; SARS-CoV-2 ; SARS-CoV-2 - genetics ; SARS-CoV-2 - metabolism ; Viral Proteins - genetics ; Viral Proteins - metabolism ; virus-host interactome
Is Part Of: Cell host & microbe, 2021-02, Vol.29 (2), p.267-280.e5
Description: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution than genome-scale studies. This approach yielded several insights, including potential virus-specific differences in Rab GTPase requirements and glycosylphosphatidylinositol (GPI) anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating coronavirus disease 2019 (COVID-19) and help prepare for future coronavirus outbreaks. [Display omitted] •SARS-CoV-2 host protein interactome CRISPR screens for SARS-CoV-2 and three coronaviruses•Parallel CRISPR screens uncover unique and shared coronavirus host factors•Numbers of interacting host proteins and functional interactors are not proportional•Identified SARS-CoV-2 host factors are expressed in relevant cells in the human airway Building upon a published SARS-CoV-2 protein interactome, Hoffmann et al. use a custom CRISPR library to determine which of these interacting host proteins are essential for infection by SARS-CoV-2 virus as well as three seasonal coronaviruses. These factors represent potential targets to combat COVID-19 and perhaps future coronavirus outbreaks.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1931-3128
EISSN: 1934-6069
DOI: 10.1016/j.chom.2020.12.009
PMID: 33357464
Source: Cell Press Free Archives
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Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors

2020 Elsevier Inc. ;Copyright © 2020 Elsevier Inc. All rights reserved. ;2020 Elsevier Inc. 2020 Elsevier Inc. ;ISSN: 1931-3128 ;EISSN: 1934-6069 ;DOI: 10.1016/j.chom.2020.12.009 ;PMID: 33357464

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