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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Li B,Clohisey SM,Chia BS,Wang B,Cui A,Eisenhaure T,Schweitzer LD,Hoover P,Parkinson NJ,Nachshon A,Smith N,Regan T,Farr D,Gutmann MU,Bukhari SI,Law A,Sangesland M,Gat-Viks I,Digard P,Vasudevan S,Lingwood D,Dockredoi
10.1038/s41467-019-13965-xsubject
Has Abstractpub_date
2020-01-09 00:00:00pages
164issue
1issn
2041-1723pii
10.1038/s41467-019-13965-xjournal_volume
11pub_type
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