Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Autor:	Haas KM; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., McGregor MJ; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Bouhaddou M; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Polacco BJ; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Kim EY; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Nguyen TT; J. David Gladstone Institutes, San Francisco, CA, 94158, USA., Newton BW; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA., Urbanowski M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Kim H; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Williams MAP; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Rezelj VV; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France., Hardy A; Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France., Fossati A; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Stevenson EJ; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Sukerman E; Division of Infectious Diseases, Oregon Health & Science University, Portland, OR, 97239, USA., Kim T; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Penugonda S; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Moreno E; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Infectious Diseases, Hospital Universitario Ramón y Cajal and IRYCIS, Madrid, Spain.; Centro de Investigación en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Braberg H; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Zhou Y; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Metreveli G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Harjai B; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Tummino TA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, USA.; Graduate Program in Pharmaceutical Sciences and Pharmacogenomics, University of California San Francisco, San Francisco, CA, 94158, USA., Melnyk JE; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Soucheray M; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Batra J; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Pache L; Infectious and Inflammatory Disease Center, Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA., Martin-Sancho L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Infectious Disease, Imperial College London, London, SW7 2BX, UK., Carlson-Stevermer J; Synthego Corporation, Redwood City, CA, 94063, USA.; Serotiny Inc., South San Francisco, CA, 94080, USA., Jureka AS; Molecular Virology and Vaccine Team, Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization & Respiratory Diseases, Centers for Disease Control & Prevention, Atlanta, GA, 30333, USA.; General Dynamics Information Technology, Federal Civilian Division, Atlanta, GA, 30329, USA., Basler CF; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Shokat KM; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA., Shoichet BK; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, USA., Shriver LP; Department of Chemistry, Washington University in St. Louis, St. Louis, MO, 63105, USA.; Center for Metabolomics and Isotope Tracing, Washington University in St. Louis, St. Louis, MO, 63105, USA., Johnson JR; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Shaw ML; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Medical Biosciences, University of the Western Cape, Bellville, 7535, Western Cape, South Africa., Chanda SK; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Roden DM; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Carter TC; Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, 54449, USA., Kottyan LC; Center of Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA., Chisholm RL; Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA., Pacheco JA; Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA., Smith ME; Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA., Schrodi SJ; Laboratory of Genetics, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, 53706, USA., Albrecht RA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Vignuzzi M; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France., Zuliani-Alvarez L; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Swaney DL; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Eckhardt M; J. David Gladstone Institutes, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA., Wolinsky SM; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., White KM; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA.; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Hultquist JF; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA. judd.hultquist@northwestern.edu.; Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. judd.hultquist@northwestern.edu.; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL, 60611, USA. judd.hultquist@northwestern.edu., Kaake RM; J. David Gladstone Institutes, San Francisco, CA, 94158, USA. robyn.kaake@ucsf.edu.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA. robyn.kaake@ucsf.edu.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA. robyn.kaake@ucsf.edu.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA. robyn.kaake@ucsf.edu., García-Sastre A; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA. adolfo.garcia-sastre@mssm.edu.; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. adolfo.garcia-sastre@mssm.edu., Krogan NJ; J. David Gladstone Institutes, San Francisco, CA, 94158, USA. nevan.krogan@ucsf.edu.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA. nevan.krogan@ucsf.edu.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, 94158, USA. nevan.krogan@ucsf.edu.; Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA, 94158, USA. nevan.krogan@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2023 Sep 27; Vol. 14 (1), pp. 6030. Date of Electronic Publication: 2023 Sep 27.
DOI:	10.1038/s41467-023-41442-z
Abstrakt:	Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. (© 2023. Springer Nature Limited.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink