Journal article
Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding
Cell host & microbe, Vol.18(6), pp.723-735
12/09/2015
DOI: 10.1016/j.chom.2015.11.002
PMCID: PMC4829074
PMID: 26651948
Abstract
Several systems-level datasets designed to dissect host-pathogen interactions during influenza A infection have been reported. However, apparent discordance among these data has hampered their full utility toward advancing mechanistic and therapeutic knowledge. To collectively reconcile these datasets, we performed a meta-analysis of data from eight published RNAi screens and integrated these data with three protein interaction datasets, including one generated within the context of this study. Further integration of these data with global virus-host interaction analyses revealed a functionally validated biochemical landscape of the influenza-host interface, which can be queried through a simplified and customizable web portal (http://www.metascape.org/IAV). Follow-up studies revealed that the putative ubiquitin ligase UBR4 associates with the viral M2 protein and promotes apical transport of viral proteins. Taken together, the integrative analysis of influenza OMICs datasets illuminates a viral-host network of high-confidence human proteins that are essential for influenza A virus replication.
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•Meta-analysis of influenza OMICs datasets reveals high-confidence virus-host interactions•Integration of orthogonal data exposes unique host and restriction factor activities•Experimental validation of virus-host circuits supports robustness of approach•The host E3 ligase UBR4 is identified as essential for virus budding and pathogenesis
Tripathi et al. have reconciled and integrated divergent influenza “OMICs” studies to reveal a functionally validated virus-host interaction network of high-confidence human proteins essential for influenza A virus replication. The authors leverage this approach to identify UBR4 as a host protein essential for virus budding and pathogenesis.
Details
- Title: Subtitle
- Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding
- Creators
- Shashank Tripathi - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAMarie O Pohl - Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, SwitzerlandYingyao Zhou - Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USAAriel Rodriguez-Frandsen - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USAGuojun Wang - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADavid A Stein - Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USAHong M Moulton - Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USAPaul DeJesus - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USAJianwei Che - Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USALubbertus C.F Mulder - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAEmilio Yángüez - Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, SwitzerlandDario Andenmatten - Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, SwitzerlandLars Pache - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USABalaji Manicassamy - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USARandy A Albrecht - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAMaria G Gonzalez - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAQuy Nguyen - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USAAbraham Brass - Microbiology and Physiological Systems (MaPS) Department, University of Massachusetts Medical School, Worcester, MA 01605, USAStephen Elledge - Department of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02127, USAMichael White - University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USASagi Shapira - Columbia University, Department of Systems Biology and Department of Microbiology and Immunology, 1130 St. Nicholas Avenue, New York, NY 10032, USANir Hacohen - Massachusetts General Hospital, 49 13th Street, Charlestown, MA 02129, USAAlexander Karlas - Max Planck Institute for Infection Biology, Charitéplatz 1, Campus Charité Mitte, 10117 Berlin, GermanyThomas F Meyer - Max Planck Institute for Infection Biology, Charitéplatz 1, Campus Charité Mitte, 10117 Berlin, GermanyMichael Shales - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USAAndre Gatorano - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USAJeffrey R Johnson - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USAGwen Jang - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USATasha Johnson - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USAErik Verschueren - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USADoug Sanders - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USANevan Krogan - University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USAMegan Shaw - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USARenate König - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USASilke Stertz - Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, SwitzerlandAdolfo García-Sastre - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USASumit K Chanda - Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.18(6), pp.723-735
- DOI
- 10.1016/j.chom.2015.11.002
- PMID
- 26651948
- PMCID
- PMC4829074
- NLM abbreviation
- Cell Host Microbe
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000060, name: NIAID, award: U19 AI106754; DOI: 10.13039/501100001711, name: Swiss National Science Foundation, award: 31003A_135278; DOI: 10.13039/501100001961, name: AXA Research Fund; DOI: 10.13039/100000002, name: NIH, award: P50 GM085764; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases of the NIH, award: 1R01AI091786; DOI: 10.13039/100000861, name: Burroughs Wellcome Fund; DOI: 10.13039/100000865, name: Bill and Melinda Gates Foundation
- Language
- English
- Date published
- 12/09/2015
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083268602771
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