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

Nat Commun. 2020 Jan 9;11(1):164. doi: 10.1038/s41467-019-13965-x.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adaptor Proteins, Signal Transducing / genetics
  • Antiviral Agents / pharmacology
  • CRISPR-Cas Systems
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • Dibenzothiepins
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Influenza A virus / pathogenicity*
  • Influenza, Human / genetics*
  • Influenza, Human / pathology*
  • Membrane Proteins / genetics
  • Methyltransferases / metabolism
  • Morpholines
  • Nerve Tissue Proteins / genetics
  • Oxazines / pharmacology
  • Pyridines / pharmacology
  • Pyridones
  • Thiepins / pharmacology
  • Triazines / pharmacology
  • Vacuolar Proton-Translocating ATPases / metabolism
  • Virus Internalization


  • Adaptor Proteins, Signal Transducing
  • Antiviral Agents
  • Ccdc115 protein, human
  • Dibenzothiepins
  • Membrane Proteins
  • Morpholines
  • Nerve Tissue Proteins
  • Oxazines
  • Pyridines
  • Pyridones
  • TMEM199 protein, human
  • Thiepins
  • Triazines
  • WDR7 protein, human
  • baloxavir
  • Methyltransferases
  • mRNA (guanine(N7))-methyltransferase
  • Vacuolar Proton-Translocating ATPases