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

Bo Li, Sara M. Clohisey, Bing Shao Chia, Bo Wang, Ang Cui, Thomas Eisenhaure, Lawrence D. Schweitzer, Paul Hoover, Nicholas J. Parkinson, Aharon Nachshon, Nikki Smith, Tim Regan, David Farr, Michael U. Gutmann, Syed Irfan Bukhari, Andrew Law, Maya Sangesland, Irit Gat-Viks, Paul Digard, Shobha Vasudevan, Daniel Lingwood, David H. Dockrell, John G. Doench, J. Kenneth Baillie () and Nir Hacohen ()
Additional contact information
Bo Li: Harvard University Virology Program, Harvfvard Medical School
Sara M. Clohisey: University of Edinburgh
Bing Shao Chia: Harvard University Virology Program, Harvfvard Medical School
Bo Wang: University of Edinburgh
Ang Cui: Broad Institute of MIT and Harvard
Thomas Eisenhaure: Broad Institute of MIT and Harvard
Lawrence D. Schweitzer: Broad Institute of MIT and Harvard
Paul Hoover: Broad Institute of MIT and Harvard
Nicholas J. Parkinson: University of Edinburgh
Aharon Nachshon: Tel Aviv University
Nikki Smith: University of Edinburgh
Tim Regan: University of Edinburgh
David Farr: University of Edinburgh
Michael U. Gutmann: University of Edinburgh
Syed Irfan Bukhari: Harvard Medical School
Andrew Law: University of Edinburgh
Maya Sangesland: MIT and Harvard University
Irit Gat-Viks: Broad Institute of MIT and Harvard
Paul Digard: University of Edinburgh
Shobha Vasudevan: Harvard Medical School
Daniel Lingwood: MIT and Harvard University
David H. Dockrell: University of Edinburgh
John G. Doench: Broad Institute of MIT and Harvard
J. Kenneth Baillie: University of Edinburgh
Nir Hacohen: Broad Institute of MIT and Harvard

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13965-x

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