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Genome-wide CRISPR screen Identifies Host Dependency Factors for Influenza A Virus Infection

Research output: Contribution to journalArticle

  • Bo Li
  • Bing Shao Chia
  • Bo Wang
  • Ang Cui
  • Thomas Eisenhaure
  • Lawrence D. Schweitzer
  • Paul Hoover
  • Aharon Nachshon
  • David Farr
  • Syed Irfan Bukhari
  • Maya Sangesland
  • Irit Gat-viks
  • Shobha Vasudevan
  • Daniel Lingwood
  • John G. Doench
  • Nir Hacohen

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http://www.nature.com/articles/s41467-019-13965-x
Original languageEnglish
JournalNature Communications
Volume11
Issue number1
Early online date9 Jan 2020
DOIs
Publication statusE-pub ahead of print - 9 Jan 2020

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 out33 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.

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