Open AccessIdentification and characterization of the role of c-terminal Src kinase in dengue virus replication
Author(s) -
Rinki Kumar,
Tanvi Agrawal,
Naseem Ahmed Khan,
Yuji Nakayama,
Guruprasad R. Medigeshi
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep30490
Subject(s) - tyrosine protein kinase csk , proto oncogene tyrosine protein kinase src , dengue virus , dengue fever , kinase , viral replication , biology , virology , tyrosine kinase , sh3 domain , small interfering rna , fyn , microbiology and biotechnology , virus , signal transduction , rna , genetics , gene
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.