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SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening

查看全文 作　　者：Tiezhu [1]Liu;Jiajia [3,4]Li;Yang [1]Liu;Yuanyuan [1]Qu;Aqian [1]Li;Chuan [1]Li;Quanfu [1]Zhang;Wei [1]Wu;Jiandong [1]Li;Yan [1,2,3,4]Liu;Dexin [1]Li;Shiwen [1,2]Wang;Mifang [1,2]Liang 高影响力作者 机构地区：[1]Key Laboratory of Medical Virology and Viral Diseases,Ministry of Health of People's Republic of China,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;[2]CDC-WIV Joint Research Center for Emerging Diseases and Biosafety,Wuhan 430071,China;[3]Department of Microbiology,Anhui Medical University,Hefei 230032,China;[4]The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China高影响力机构 出　　处：《Virologica Sinica》索引2019年第34卷第5期,共13页高影响力期刊 基　　金：supported by the National Key Project for Infectious Disease from the Ministry of Science and Technology (Grant No. 2018ZX10711-001) 摘　　要：Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized.Using a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV infection.An SNX11-KO HeLa cell line was established,and SFTSV replication was significantly reduced.The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi apparatus.pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO cells.Overall,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11.Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery. 关 键 词：CRISPR screen Severe fever with thrombocytopenia syndrome virus(SFTSV) Host factor Sorting nexin 11(SNX11)
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