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Virology. 2015 Oct;484:241-50. doi: 10.1016/j.virol.2015.06.015. Epub 2015 Jun 26.

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

Author information

1
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
2
Department of Microbiology, La Trobe University, Melbourne, VIC, Australia.
3
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Electronic address: jason.mackenzie@unimelb.edu.au.

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 (WNVKUN) replication complex (RC) but not to the dengue virus serotype 2 strain New Guinea C (DENVNGC) RC. We show that prolonged chemical inhibition of serine palmitoyltransferase with myriocin had a significant deleterious effect on WNVKUN replication but enhanced DENVNGC replication. Additionally, inhibition of ceramide synthase with Fumonisin B1 had a detrimental effect on WNVKUN replication and release of infectious virus particles but contrastingly an enhancing effect on DENVNGC replication and virus production. These observations suggest that ceramide production via the de novo and salvage pathway is a requirement for WNVKUN replication but inhibitory for DENVNGC replication. Thus, although these two viruses are from the same genus, they have a differential ceramide requirement for replication.

KEYWORDS:

Ceramide; Dengue virus; Virus replication; West Nile virus

PMID:
26122470
DOI:
10.1016/j.virol.2015.06.015
[Indexed for MEDLINE]
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