Differential utilisation of ceramide during replication of the flaviviruses West Nile and dengue virus

Abstract It is well established that +ssRNA viruses manipulate cellular lipid homoeostasis and distribution to facilitate efficient replication. Here, we show that the cellular lipid ceramide is redistributed to the West Nile virus strain Kunjin virus (WNV KUN ) replication complex (RC) but not to the dengue virus serotype 2 strain New Guinea C (DENV NGC ) RC. We show that prolonged chemical inhibition of serine palmitoyltransferase with myriocin had a significant deleterious effect on WNV KUN replication but enhanced DENV NGC replication. Additionally, inhibition of ceramide synthase with Fumonisin B 1 had a detrimental effect on WNV KUN replication and release of infectious virus particles but contrastingly an enhancing effect on DENV NGC replication and virus production. These observations suggest that ceramide production via the de novo and salvage pathway is a requirement for WNV KUN replication but inhibitory for DENV NGC replication. Thus, although these two viruses are from the same genus, they have a differential ceramide requirement for replication.