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Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication
Open accessAbstract
The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens.
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Metadata
- Authors
- Han, J., Perez, J. T., Chen, C., Li, Y., Benitez, A., Kandasamy, M., Lee, Y., Andrade, J., tenOever, B., & Manicassamy, B.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 23
- Issue
- 2
- Pages
- 596-607
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2797613160
- Cited by
- 266
- References
- 47
- FWCI
- 22.84
- Type
- journal article
- Language
- en
- Open access
- gold
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