TitleMeta- and Orthogonal Integration of Influenza "OMICs" Data Defines a Role for UBR4 in Virus Budding.
Publication TypeJournal Article
Year of Publication2015
AuthorsTripathi, S, Pohl, MO, Zhou, Y, Rodriguez-Frandsen, A, Wang, G, Stein, DA, Moulton, HM, DeJesus, P, Che, J, Mulder, LCF, Yángüez, E, Andenmatten, D, Pache, L, Manicassamy, B, Albrecht, RA, Gonzalez, MG, Nguyen, Q, Brass, A, Elledge, S, White, M, Shapira, S, Hacohen, N, Karlas, A, Meyer, TF, Shales, M, Gatorano, A, Johnson, JR, Jang, G, Johnson, T, Verschueren, E, Sanders, D, Krogan, N, Shaw, M, König, R, Stertz, S, García-Sastre, A, Chanda, SK
JournalCell Host Microbe
Date Published2015 Dec 09
KeywordsAnimals, Calmodulin-Binding Proteins, Cell Line, Computational Biology, Cytoskeletal Proteins, Flow Cytometry, Host-Pathogen Interactions, Humans, Immunoprecipitation, Influenza A virus, Mice, Inbred BALB C, Microscopy, Fluorescence, Protein Binding, Protein Interaction Maps, Protein Transport, Ubiquitin-Protein Ligases, Viral Matrix Proteins, Virus Release

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.

Alternate JournalCell Host Microbe
PubMed ID26651948
PubMed Central IDPMC4829074
Grant ListNIH P50 GM085764 / GM / NIGMS NIH HHS / United States
R01 AI091786 / AI / NIAID NIH HHS / United States
R35 CA197717 / CA / NCI NIH HHS / United States
1R01AI091786 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
U19 AI106754 / AI / NIAID NIH HHS / United States
R01 GM109018 / GM / NIGMS NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States