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Nat Commun DOI:10.1038/s41467-019-13965-x

Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.

Publication TypeJournal Article
Year of Publication2020
AuthorsLi, B, Clohisey, SM, Chia, BShao, Wang, B, Cui, A, Eisenhaure, T, Schweitzer, LD, Hoover, P, Parkinson, NJ, Nachshon, A, Smith, N, Regan, T, Farr, D, Gutmann, MU, Bukhari, SIrfan, Law, A, Sangesland, M, Gat-Viks, I, Digard, P, Vasudevan, S, Lingwood, D, Dockrell, DH, Doench, JG, J Baillie, K, Hacohen, N
JournalNat Commun
Volume11
Issue1
Pages164
Date Published2020 Jan 09
ISSN2041-1723
Abstract

Host dependency factors that are required for influenza A virus infection may serve as therapeutic targets as the virus is less likely to bypass them under drug-mediated selection pressure. Previous attempts to identify host factors have produced largely divergent results, with few overlapping hits across different studies. Here, we perform a genome-wide CRISPR/Cas9 screen and devise a new approach, meta-analysis by information content (MAIC) to systematically combine our results with prior evidence for influenza host factors. MAIC out-performs other meta-analysis methods when using our CRISPR screen as validation data. We validate the host factors, WDR7, CCDC115 and TMEM199, demonstrating that these genes are essential for viral entry and regulation of V-type ATPase assembly. We also find that CMTR1, a human mRNA cap methyltransferase, is required for efficient viral cap snatching and regulation of a cell autonomous immune response, and provides synergistic protection with the influenza endonuclease inhibitor Xofluza.

DOI10.1038/s41467-019-13965-x
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31919360?dopt=Abstract

Alternate JournalNat Commun
PubMed ID31919360
Grant List103258/Z/13/Z / / Wellcome Trust (Wellcome) /
NIH P50HG006193 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /