ANTIVIRAL THERAPY OF CHIKUNGUNYA VIRUS INFECTION

Abstract

In this study, a panel of proteasome inhibitors was shown to inhibit CHIKV infection. Bortezomib, a proteasome inhibitor selected for downstream studies, was shown to inhibit CHIKV at an early, post-entry stage. Inhibition of the proteasome by bortezomib resulted in elevations of the viral polymerase and suppression of levels of all other CHIKV proteins. CHIKV RNA levels showed minor increases towards later timepoints, while the percentage infectivity of virus particles was reduced upon bortezomib treatment. We also developed a humanized mouse model of CHIKV infection. Viral load in infected humanized mice lasted about a week in the serum and was prolonged in the liver, spleen and hind limb muscles. Histology data showed evidence of chronic pathology at late time-points. CHIKV infection was accompanied by a robust human immune response during the acute and chronic phases. Finally, treatment of infected mice with bortezomib suppressed viremia only on the first day post-infection.