title: Identification and characterization of the role of c-terminal Src kinase in dengue virus replication.
abstract: We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication. Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry. Csk partially colocalized with viral replication compartments. Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes. Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases. Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication. Overexpression studies suggest an important role for the kinase and SH3 domains in this process. Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Haryana, India.|Department of Biotechnology, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
authors.forename: Rinki
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Haryana, India.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Agrawal
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Haryana, India.
authors.forename: Naseem Ahmed
authors.initials: NA
authors.lastname: Khan
authors.affiliation: Department of Biochemistry &Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Haryana, India.
authors.forename: Guruprasad R
authors.initials: GR
authors.lastname: Medigeshi
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D003715:Dengue / Q000201:enzymology / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D013329:Structure-Activity Relationship; D014779:Virus Replication; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human