title: 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 (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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
authors.forename: Turgut E
authors.initials: TE
authors.lastname: Aktepe
authors.affiliation: Department of Microbiology, La Trobe University, Melbourne, VIC, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Pham
authors.affiliation: 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.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Mackenzie
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001482:Base Composition; D002518:Ceramides / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000502:physiology*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D037341:Fumonisins / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D051102:Serine C-Palmitoyltransferase / Q000037:antagonists & inhibitors; D014709:Vero Cells; D014779:Virus Replication; D014902:West Nile virus / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D037341:Fumonisins; C056933:fumonisin B1; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D051102:Serine C-Palmitoyltransferase; C001996:thermozymocidin
keywords: Ceramide; Dengue virus; Virus replication; West Nile virus