Kinome siRNA screen identifies novel cell-type specific dengue host target genes.
Dengue is a global emerging infectious disease, with no specific treatment available. To identify novel human host cell targets important for dengue virus infection and replication, an image-based high-throughput siRNA assay screening of a human kinome siRNA library was conducted using human hepatocyte cell line Huh7 infected with a recent dengue serotype 2 virus isolate BR DEN2 01-01. In the primary siRNA screening of 779 kinase-related genes, knockdown of 22 genes showed a reduction in DENV-2 infection. Conversely, knockdown of 8 genes enhanced viral infection. To assess host cell specificity, the confirmed hits were tested in the DENV-infected monocytic cell line U937. While the expression of EIF2AK3, ETNK2 and SMAD7 was regulated in both cell lines after infection, most kinases were hepatocyte-specific. Monocytic cells represent initial targets of infection and an antiviral treatment targeting these cells is probably most effective to reduce initial viral load. In turn, infection of the liver could contribute to pathogenesis, and the novel hepatocyte-specific human targets identified here could be important for dengue infection and pathogenesis.
['Kwon|Yong-Jun|YJ|', 'Heo|Jinyeong|J|', 'Wong|Hazel E E|HE|', 'Cruz|Deu John M|DJ|', 'Velumani|Sumathy|S|', 'da Silva|Camila T|CT|', 'Mosimann|Ana Luiza P|AL|', 'Duarte Dos Santos|Claudia N|CN|', 'Freitas-Junior|Lucio H|LH|', 'Fink|Katja|K|']
D000998:Antiviral Agents D002460:Cell Line D003715:Dengue D003716:Dengue Virus D022781:Hepatocytes D057166:High-Throughput Screening Assays D054884:Host-Pathogen Interactions D006801:Humans D017853:Phosphotransferases (Alcohol Group Acceptor) D011494:Protein Kinases D034622:RNA Interference D034741:RNA, Small Interfering D051906:Smad7 Protein D014779:Virus Replication D019892:eIF-2 Kinase
siRNA Dengue Host cell targets Kinase