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

Shashank Tripathi, Marie O. Pohl, Yingyao Zhou, Ariel Rodriguez-Frandsen, Guojun Wang, David A. Stein, Hong M. Moulton, Paul Dejesus, Jianwei Che, Lubbertus C.F. Mulder, Emilio Yángüez, Dario Andenmatten, Lars Pache, Balaji Manicassamy, Randy A. Albrecht, Maria G. Gonzalez, Quy Nguyen, Abraham Brass, Stephen Elledge, Michael WhiteSagi Shapira, Nir Hacohen, Alexander Karlas, Thomas F. Meyer, Michael Shales, Andre Gatorano, Jeffrey R. Johnson, Gwen Jang, Tasha Johnson, Erik Verschueren, Doug Sanders, Nevan Krogan, Megan Shaw, Renate König, Silke Stertz, Adolfo García-Sastre, Sumit K. Chanda

Research output: Contribution to journalArticlepeer-review

688 Scopus citations

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)723-735
Number of pages13
JournalCell Host and Microbe
Volume18
Issue number6
DOIs
StatePublished - 1 Dec 2015

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