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.