Role of human tyrosine kinases in dengue virus life-cycle

Abstract

Dengue virus is a pathogen of global concern and infects about 400 million humans worldwide. Host cellular factors play an essential role at every stage of dengue life-cycle, nevertheless, very few of cellular factors that are necessary for dengue virus infection have been identified. We used a human tyrosine kinase siRNA library to identify tyrosine kinases involved in dengue virus life-cycle. C-terminal Src kinase¬ (csk) was one of the positive hits identified in primary siRNA screening. Knock-down of csk by specific siRNA reduced dengue virus titers in the supernatants. Inhibition of csk by a chemical inhibitor reduced dengue virus titers at 24 hrs post infection. Dengue infection led to increase in the phosphorylation of csk suggesting activation of csk during infection. ¬Csk knock-down by siRNAs also led to reduction in replication of Japanese encephalitis virus a related member of flavivirus genus suggesting that csk is a host factor that is involved at later stages of flavivirus life-cycle.