Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection
| Autor: | Syed I. A. Bukhari, Sara Clohisey, John G. Doench, Paul Hoover, Paul Digard, Nicholas J. Parkinson, Daniel Lingwood, Maya Sangesland, Bo Wang, Tim Regan, Thomas Eisenhaure, Nir Hacohen, Irit Gat-Viks, Shobha Vasudevan, Bo Li, Nikki Smith, Lawrence D. Schweitzer, David H. Dockrell, David Farr, Bing Shao Chia, Michael U. Gutmann, Andy Law, Ang Cui, J Kenneth Baillie, Aharon Nachshon |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CRISPR-Cas9 genome editing Pyridines viruses General Physics and Astronomy medicine.disease_cause Genome 0302 clinical medicine Influenza A virus CRISPR Clustered Regularly Interspaced Short Palindromic Repeats lcsh:Science Multidisciplinary Triazines 3. Good health Host-Pathogen Interactions Thiepins Dibenzothiepins Vacuolar Proton-Translocating ATPases Pyridones Science Morpholines Nerve Tissue Proteins Computational biology Biology Antiviral Agents General Biochemistry Genetics and Molecular Biology Virus Article Cap snatching Cell Line 03 medical and health sciences Viral entry Influenza Human Oxazines medicine Humans Genetic Predisposition to Disease Adaptor Proteins Signal Transducing Cas9 Host (biology) Membrane Proteins General Chemistry Methyltransferases Virus Internalization 030104 developmental biology A549 Cells lcsh:Q CRISPR-Cas Systems Influenza virus 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) Li, B, Clohisey, S M, Chia, B S, Wang, B, Cui, A, Eisenhaure, T, Schweitzer, L D, Hoover, P, Parkinson, N J, Nachshon, A, Smith, N, Regan, T, Farr, D, Gutmann, M U, Bukhari, S I, Law, A, Sangesland, M, Gat-viks, I, Digard, P, Vasudevan, S, Lingwood, D, Dockrell, D H, Doench, J G, Baillie, J K & Hacohen, N 2020, ' Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection ', Nature Communications, vol. 11, no. 1, 164 . https://doi.org/10.1038/s41467-019-13965-x |
| ISSN: | 2041-1723 |
| Popis: | 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. Here, Li et al. perform a genome-wide CRISPR screen to identify host dependency factors for influenza A virus infection and show that the host mRNA cap methyltransferase CMTR1 is important for viral cap snatching and that it affects expression of antiviral genes. |
| Databáze: | OpenAIRE |
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