title: Impaired cholesterol biosynthesis in a neuronal cell line persistently infected with measles virus.
abstract: Measles virus remains a substantial cause of morbidity and mortality, producing acute infection with a potential for development of viral persistence. To study the events underlying acute and persistent measles virus infection, we performed a global transcriptional analysis on murine neuroblastoma cells that were acutely or persistently infected with measles virus. In general, we found that acute infection induced significantly more gene expression changes than did persistent infection. A functional enrichment analysis to identify which host pathways were perturbed during each of these infections identified several pathways related to cholesterol biosynthesis, including cholesterol metabolic processes, hydroxymethylglutaryl-coenzyme A (CoA) reductase activity, and acetyl-CoA C-acetyltransferase activity. We also found that measles virus colocalized to lipid rafts in both acute and persistent infection models and that the majority of genes associated with cholesterol synthesis were downregulated in persistent infection relative to acute infection, suggesting a possible link with the defective viral budding in persistent infection. Further, we found that pharmacological inhibition of cholesterol synthesis resulted in the inhibition of viral budding during acute infection. In summary, persistent measles viral infection was associated with decreased cholesterol synthesis, a lower abundance of cholesterol and lipid rafts in the cell membrane, and inhibition of giant-cell formation and release of viral progeny.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington 98195-8070, USA.
authors.forename: Shahar
authors.initials: S
authors.lastname: Robinzon
authors.forename: Avis
authors.initials: A
authors.lastname: Dafa-Berger
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Dyer
authors.forename: Bryan
authors.initials: B
authors.lastname: Paeper
authors.forename: Sean C
authors.initials: SC
authors.lastname: Proll
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Teal
authors.forename: Slava
authors.initials: S
authors.lastname: Rom
authors.forename: Daniel
authors.initials: D
authors.lastname: Fishman
authors.forename: Bracha
authors.initials: B
authors.lastname: Rager-Zisman
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D000208:Acute Disease; D000818:Animals; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008459:Measles virus / Q000502:physiology*; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D002784:Cholesterol; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases