This project examines the impact of dynein inhibition on Japanese encephalitis virus (JEV) infectious cycle. Several Flaviviruses (JEV, West Nile virus, yellow fever virus, Zika virus) show alteration of their infectious cycle in the presence of a small molecule inhibitor Ciliobrevin D, which specifically inhibits ATPase activity of cytoplasmic dynein.
We recently identified a time window comprised between 9 and 15h pi during which dynein is essential to JEV infectious cycle. JEV replication is indirectly affected when ATPase activity of dynein is inhibited, with an inhibition of translation and a decrease in infectious particles production, while specific infectivity is increased.
Thus dynein seems to play a role in JEV viral assembly and secretion steps. Moreover, ATPase activity of dynein is necessary for the transport of JEV capsid protein to the nucleus (J.Basset et al, in preparation).