Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication.
Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication.
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DOI：
10.1016/j.celrep.2018.03.045
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发表时间：
2018-04-10
期刊：
影响因子：
8.8
通讯作者：
Manicassamy B
中科院分区：
文献类型：
--
作者：
Han J;Perez JT;Chen C;Li Y;Benitez A;Kandasamy M;Lee Y;Andrade J;tenOever B;Manicassamy B
人畜共患病宿主中甲型流感病毒的出现对人类健康构成了极大的威胁。由于季节性疫苗对人畜共患病毒株无效，并且新传播的病毒可迅速获得耐药性，因此仍需要针对IAV的宿主定向治疗。在这里，我们在人类肺上皮细胞中用禽H5 N1毒株的人类分离株进行了基因组规模的CRISPR/Cas9敲除筛选。参与唾液酸生物合成和相关糖基化途径的几个基因在H5 N1选择后高度富集，包括SLC 35 A1，IAV受体表达和病毒进入所必需的唾液酸转运蛋白。重要的是，我们已经确定Capicua（CIC）是细胞固有免疫的负调节因子，因为CIC的缺失导致抗病毒应答增强和多种病毒复制受限。因此，我们的研究表明，CRISPR/Cas9系统可用于发现对细胞内病原体复制至关重要的宿主因子。使用全基因组CRISPR/Cas9筛选，Han等人证明了主要的命中，唾液酸转运蛋白SLC 35 A1，是IAV进入的重要宿主因子。此外，他们确定了DNA结合转录抑制因子CIC作为细胞内在免疫的负调节因子。
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. 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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DOI：
10.1073/pnas.0405172102
发表时间：
2004-12-28
影响因子：
11.1
作者：
Chu, VC;Whittaker, GR
通讯作者：
Whittaker, GR
DOI：
10.1126/science.aaf1220
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Orchard RC;Wilen CB;Doench JG;Baldridge MT;McCune BT;Lee YC;Lee S;Pruett-Miller SM;Nelson CA;Fremont DH;Virgin HW
通讯作者：
Virgin HW
影响因子：
4.6
作者：
Ajuria, Leiore;Nieva, Claudia;Jimenez, Gerardo
通讯作者：
Jimenez, Gerardo
影响因子：
4.6
作者：
Kim E;Park S;Choi N;Lee J;Yoe J;Kim S;Jung HY;Kim KT;Kang H;Fryer JD;Zoghbi HY;Hwang D;Lee Y
通讯作者：
Lee Y
影响因子：
21.3
作者：
Castillo-Lluva, Sonia;Tatham, Michael H.;Jones, Richard C.;Jaffray, Ellis G.;Edmondson, Ricky D.;Hay, Ronald T.;Malliri, Angeliki
通讯作者：
Malliri, Angeliki