Inhibition of protein kinase C promotes dengue virus replication - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Virology Journal Année : 2016

Inhibition of protein kinase C promotes dengue virus replication

Résumé

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.
Fichier principal
Vignette du fichier
document(1).pdf (2.12 Mo) Télécharger le fichier
Origine Publication financée par une institution
Loading...

Dates et versions

pasteur-02082898 , version 1 (28-03-2019)

Licence

Identifiants

Citer

Warobon Noppakunmongkolchai, Teera Poyomtip, Thichakorn Jittawuttipoka, Natthanej Luplertlop, Anavaj Sakuntabhai, et al.. Inhibition of protein kinase C promotes dengue virus replication. Virology Journal, 2016, 13, pp.35. ⟨10.1186/s12985-016-0494-6⟩. ⟨pasteur-02082898⟩

Collections

PASTEUR CNRS
39 Consultations
84 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More