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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 10; 29(2):267-280.e5.CH

Abstract

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.

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Authors+Show Affiliations

Hoffmann HH
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Sánchez-Rivera FJ
Cancer Biology and Genetics, MSKCC New York, NY 10065, USA.
Schneider WM
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Luna JM
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Soto-Feliciano YM
Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, NY 10065, USA.
Ashbrook AW
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Le Pen J
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Leal AA
Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016 USA.
Ricardo-Lax I
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Michailidis E
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Hao Y
Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016 USA.
Stenzel AF
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Peace A
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Zuber J
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria; Medical University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Allis CD
Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, NY 10065, USA.
Lowe SW
Cancer Biology and Genetics, MSKCC New York, NY 10065, USA.
MacDonald MR
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Poirier JT
Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016 USA. Electronic address: john.poirier@nyulangone.org.
Rice CM
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. Electronic address: ricec@rockefeller.edu.

MeSH

COVID-19CRISPR-Cas SystemsCoronavirus 229E, HumanCoronavirus NL63, HumanCoronavirus OC43, HumanGenes, ViralHost-Pathogen InteractionsHumansSARS-CoV-2Viral Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

33357464

Citation

Hoffmann, H-Heinrich, et al. "Functional Interrogation of a SARS-CoV-2 Host Protein Interactome Identifies Unique and Shared Coronavirus Host Factors." Cell Host & Microbe, vol. 29, no. 2, 2021, pp. 267-280.e5.
Hoffmann HH, Sánchez-Rivera FJ, Schneider WM, et al. Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors. Cell Host Microbe. 2021;29(2):267-280.e5.
Hoffmann, H. H., Sánchez-Rivera, F. J., Schneider, W. M., Luna, J. M., Soto-Feliciano, Y. M., Ashbrook, A. W., Le Pen, J., Leal, A. A., Ricardo-Lax, I., Michailidis, E., Hao, Y., Stenzel, A. F., Peace, A., Zuber, J., Allis, C. D., Lowe, S. W., MacDonald, M. R., Poirier, J. T., & Rice, C. M. (2021). Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors. Cell Host & Microbe, 29(2), 267-e5. https://doi.org/10.1016/j.chom.2020.12.009
Hoffmann HH, et al. Functional Interrogation of a SARS-CoV-2 Host Protein Interactome Identifies Unique and Shared Coronavirus Host Factors. Cell Host Microbe. 2021 02 10;29(2):267-280.e5. PubMed PMID: 33357464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors. AU - Hoffmann,H-Heinrich, AU - Sánchez-Rivera,Francisco J, AU - Schneider,William M, AU - Luna,Joseph M, AU - Soto-Feliciano,Yadira M, AU - Ashbrook,Alison W, AU - Le Pen,Jérémie, AU - Leal,Andrew A, AU - Ricardo-Lax,Inna, AU - Michailidis,Eleftherios, AU - Hao,Yuan, AU - Stenzel,Ansgar F, AU - Peace,Avery, AU - Zuber,Johannes, AU - Allis,C David, AU - Lowe,Scott W, AU - MacDonald,Margaret R, AU - Poirier,John T, AU - Rice,Charles M, Y1 - 2020/12/16/ PY - 2020/09/11/received PY - 2020/11/13/revised PY - 2020/12/09/accepted PY - 2020/12/29/pubmed PY - 2021/3/4/medline PY - 2020/12/28/entrez KW - COVID-19 KW - CRISPR KW - HCoV KW - HCoV-229E KW - HCoV-NL63 KW - HCoV-OC43 KW - SARS-CoV-2 KW - coronavirus KW - virus-host interactome SP - 267 EP - 280.e5 JF - Cell host & microbe JO - Cell Host Microbe VL - 29 IS - 2 N2 - 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. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/33357464/Functional_interrogation_of_a_SARS_CoV_2_host_protein_interactome_identifies_unique_and_shared_coronavirus_host_factors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-3128(20)30671-5 DB - PRIME DP - Unbound Medicine ER -