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Cell Host Microbe. 2015 Dec 9;18(6):723-35. doi: 10.1016/j.chom.2015.11.002.

Meta- and Orthogonal Integration of Influenza "OMICs" Data Defines a Role for UBR4 in Virus Budding.

Author information

  • 1Department 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.
  • 2Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • 3Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
  • 4Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • 5Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 6Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
  • 7Microbiology and Physiological Systems (MaPS) Department, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • 8Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02127, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • 9University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
  • 10Columbia University, Department of Systems Biology and Department of Microbiology and Immunology, 1130 St. Nicholas Avenue, New York, NY 10032, USA.
  • 11Massachusetts General Hospital, 49 13th Street, Charlestown, MA 02129, USA.
  • 12Max Planck Institute for Infection Biology, Charitéplatz 1, Campus Charité Mitte, 10117 Berlin, Germany.
  • 13University of California, San Francisco, 1700 4th Street, Byers Hall 309, San Francisco, CA 94158, USA.
  • 14Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Host-Pathogen Interactions, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225 Langen, Germany; German Center for Infection Research (DZIF), 63225 Langen, Germany. Electronic address: renate.koenig@pei.de.
  • 15Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: stertz.silke@virology.uzh.ch.
  • 16Department 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 Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: adolfo.garcia-sastre@mssm.edu.
  • 17Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: schanda@sbpdiscovery.org.

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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PMID:
26651948
PMCID:
PMC4829074
DOI:
10.1016/j.chom.2015.11.002
[PubMed - indexed for MEDLINE]
Free PMC Article
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