Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication
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 IAV...
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Veröffentlicht in: | Cell reports (Cambridge) 2018-04, Vol.23 (2), p.596-607 |
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Sprache: | eng |
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Zusammenfassung: | 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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•Genome-wide CRISPR/Cas9 screen used to identify pro-viral IAV host factors•Host factors identified in viral entry and regulation of antiviral gene expression•Sialic acid transporter SLC35A1 is essential for viral receptor expression•Transcriptional repressor CIC is a negative regulator of cell-intrinsic immunity
Using a genome-wide CRISPR/Cas9 screen, Han et al. demonstrate that the major hit, the sialic acid transporter SLC35A1, is an essential host factor for IAV entry. In addition, they identify the DNA-binding transcriptional repressor CIC as a negative regulator of cell-intrinsic immunity. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2018.03.045 |