tetano
Editor, Senior Moderator
Nat Commun. 2020 Jan 9;11(1):164. doi: 10.1038/s41467-019-13965-x. [h=1]Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.[/h]
Li B[SUP]1,[/SUP][SUP]2[/SUP], Clohisey SM[SUP]3[/SUP], Chia BS[SUP]1,[/SUP][SUP]2[/SUP], Wang B[SUP]3[/SUP], Cui A[SUP]2,[/SUP][SUP]4[/SUP], Eisenhaure T[SUP]2[/SUP], Schweitzer LD[SUP]2[/SUP], Hoover P[SUP]2[/SUP], Parkinson NJ[SUP]3[/SUP], Nachshon A[SUP]5[/SUP], Smith N[SUP]3[/SUP], Regan T[SUP]3[/SUP], Farr D[SUP]3[/SUP], Gutmann MU[SUP]6[/SUP], Bukhari SI[SUP]7[/SUP], Law A[SUP]3[/SUP], Sangesland M[SUP]8[/SUP], Gat-Viks I[SUP]2,[/SUP][SUP]5[/SUP], Digard P[SUP]3[/SUP], Vasudevan S[SUP]7[/SUP], Lingwood D[SUP]8[/SUP], Dockrell DH[SUP]9[/SUP], Doench JG[SUP]2[/SUP], Baillie JK[SUP]10,[/SUP][SUP]11[/SUP], Hacohen N[SUP]12,[/SUP][SUP]13[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 31919360 PMCID: PMC6952391 DOI: 10.1038/s41467-019-13965-x
Free PMC Article
Li B[SUP]1,[/SUP][SUP]2[/SUP], Clohisey SM[SUP]3[/SUP], Chia BS[SUP]1,[/SUP][SUP]2[/SUP], Wang B[SUP]3[/SUP], Cui A[SUP]2,[/SUP][SUP]4[/SUP], Eisenhaure T[SUP]2[/SUP], Schweitzer LD[SUP]2[/SUP], Hoover P[SUP]2[/SUP], Parkinson NJ[SUP]3[/SUP], Nachshon A[SUP]5[/SUP], Smith N[SUP]3[/SUP], Regan T[SUP]3[/SUP], Farr D[SUP]3[/SUP], Gutmann MU[SUP]6[/SUP], Bukhari SI[SUP]7[/SUP], Law A[SUP]3[/SUP], Sangesland M[SUP]8[/SUP], Gat-Viks I[SUP]2,[/SUP][SUP]5[/SUP], Digard P[SUP]3[/SUP], Vasudevan S[SUP]7[/SUP], Lingwood D[SUP]8[/SUP], Dockrell DH[SUP]9[/SUP], Doench JG[SUP]2[/SUP], Baillie JK[SUP]10,[/SUP][SUP]11[/SUP], Hacohen N[SUP]12,[/SUP][SUP]13[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 31919360 PMCID: PMC6952391 DOI: 10.1038/s41467-019-13965-x
Free PMC Article