Warobon NoppakunmongkolchaiTeera PoyomtipThichakorn JittawuttipokaNatthanej LuplertlopAnavaj SakuntabhaiSarin ChimnaronkSiwanon JirawatnotaiRutaiwan TohtongMahidol UniversityInstitut Pasteur, ParisCNRS Centre National de la Recherche ScientifiqueFaculty of Medicine, Siriraj Hospital, Mahidol University2018-12-112019-03-142018-12-112019-03-142016-03-01Virology Journal. Vol.13, No.1 (2016)1743422X2-s2.0-84978731786https://repository.li.mahidol.ac.th/handle/123456789/40877© 2016 Noppakunmongkolchai et al. Background: Dengue virus (DENV) is a member of the Flaviviridae family, transmitted to human via mosquito. DENV infection is common in tropical areas and occasionally causes life-threatening symptoms. DENV contains a relatively short positive-stranded RNA genome, which encodes ten viral proteins. Thus, the viral life cycle is necessarily rely on or regulated by host factors. Methods: In silico analyses in conjunction with in vitro kinase assay were used to study kinases that potentially phosphorylate DENV NS5. Potential kinase was inhibited or activated by a specific inhibitor (or siRNA), or an activator. Results of the inhibition and activation on viral entry/replication and host cell survival were examined. Results: Our in silico analyses indicated that the non-structural protein 5 (NS5), especially the RNA-dependent RNA polymerase (RdRp) domain, contains conserved phosphorylation sites for protein kinase C (PKC). Phosphorylation of NS5 RdRp was further verified by PKC in vitro kinase assay. Inhibitions of PKC by a PKC-specific chemical inhibitor or siRNA suppressed NS5 phosphorylation in vivo, increased viral replication and reduced viability of the DENV-infected cells. In contrary, activation of PKC effectively suppressed intracellular viral number. Conclusions: These results indicated that PKC may act as a restricting mechanism that modulates the DENV replication and represses the viral outburst in the host cells.Mahidol UniversityImmunology and MicrobiologyArticleSCOPUS10.1186/s12985-016-0494-6