Global siRNA Screen Reveals Critical Human Host Factors of SARS-CoV-2 Multicycle Replication.

Autor:	Yin X; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China., Pu Y; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, USA., Yuan S; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Pache L; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Churas C; Department of Medicine, University of California San Diego, La Jolla, USA., Weston S; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, USA., Riva L; Calibr-Skaggs at Scripps Research Institute, La Jolla, USA., Simons LM; Division of Infectious Diseases, Departments of Medicine and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, USA., Cisneros WJ; Division of Infectious Diseases, Departments of Medicine and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, USA., Clausen T; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, USA., De Jesus PD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, USA., Kim HN; Molecular Surface Interaction Laboratory, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, New South Wales, Australia., Fuentes D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, USA., Whitelock J; Molecular Surface Interaction Laboratory, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, New South Wales, Australia., Esko J; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, USA., Lord M; Molecular Surface Interaction Laboratory, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, New South Wales, Australia., Mena I; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, USA., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, USA; The Tisch Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, USA; The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, USA., Hultquist JF; Division of Infectious Diseases, Departments of Medicine and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, USA., Frieman MB; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, USA., Ideker T; Department of Medicine, University of California San Diego, La Jolla, USA.; Department of Computer Science and Engineering, University of California San Diego, La Jolla, USA., Pratt D; Department of Medicine, University of California San Diego, La Jolla, USA., Martin-Sancho L; Department of Infectious Disease, Imperial College London, London, United Kingdom., Chanda SK; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 10. Date of Electronic Publication: 2024 Jul 10.
DOI:	10.1101/2024.07.10.602835
Abstrakt:	Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased towards the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published datasets to reveal pathways supported by orthogonal datasets, including transcriptional regulation, epigenetic modifications, and MAPK signalling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 27 proteins that were determined to impact assembly and release. Additionally, a subset of proteins were tested across other coronaviruses revealing 17 potential pan-coronavirus targets. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry, and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo . These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals. Competing Interests: COMPETING INTERESTS STATEMENT J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences, and is a paid consultant for Merck. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, Astrazeneca and Novavax. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. All other authors declare no competing interests.
Databáze:	MEDLINE
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