Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding
By Shashank Tripathi, M. Pohl, Yingyao Zhou, A. Rodriguez-Frandsen, Guojun Wang, D. A. Stein, H. Moulton, Paul DeJesus, Jianwei Che, L. Mulder and 27 more. Cell Host and Microbe, 2015
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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.
Subfields: Epidemiology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/8040f39dfb53110b5e8e3691adcd2b0152ae2a16
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Citations in the corpus
- Zika virus targets human STAT2 to inhibit type I interferon signaling (2016, background): “To investigate whether ZIKV-induced degradation of STAT2 has a similar requirement for UBR4, we infected 293T cells that have been genetically edited by CRISPR/Cas9 to knock out UBR4 expression (Tripathi et al., 2015) and determined STAT2 levels.”
- g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update) (2019, methodology): “There are a several functional enrichment analysis tools such as Enrichr (1), WebGestalt (2), Metascape (3), KOBAS (4) and AgriGO (5) suitable for positioning the novel findings against the body of previous knowledge.”