tetano
Editor, Senior Moderator
Cell Rep. 2018 Apr 10;23(2):596-607. doi: 10.1016/j.celrep.2018.03.045.
[h=1]Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication.[/h] Han J[SUP]1[/SUP], Perez JT[SUP]1[/SUP], Chen C[SUP]1[/SUP], Li Y[SUP]2[/SUP], Benitez A[SUP]3[/SUP], Kandasamy M[SUP]1[/SUP], Lee Y[SUP]4[/SUP], Andrade J[SUP]2[/SUP], tenOever B[SUP]3[/SUP], Manicassamy B[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] CIC; CRISPR/Cas9 screen; Capicua; GeCKO; H5N1; SLC35A1; cell-intrinsic immunity; host factors; influenza virus; sialic acid pathway
PMID: 29642015 DOI: 10.1016/j.celrep.2018.03.045
[h=1]Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication.[/h] Han J[SUP]1[/SUP], Perez JT[SUP]1[/SUP], Chen C[SUP]1[/SUP], Li Y[SUP]2[/SUP], Benitez A[SUP]3[/SUP], Kandasamy M[SUP]1[/SUP], Lee Y[SUP]4[/SUP], Andrade J[SUP]2[/SUP], tenOever B[SUP]3[/SUP], Manicassamy B[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] CIC; CRISPR/Cas9 screen; Capicua; GeCKO; H5N1; SLC35A1; cell-intrinsic immunity; host factors; influenza virus; sialic acid pathway
PMID: 29642015 DOI: 10.1016/j.celrep.2018.03.045