The Role of Cholesterol Pathways in Norovirus Replication

Norwalk virus (NV) is a prototype strain of the noroviruses (family Caliciviridae) which have emerged as major causes of acute gastroenteritis worldwide. We have developed NV replicon systems using reporter proteins such as a neomycin resistant protein (NV replicon-bearing cells) and a green fluorescent protein (pNV-GFP), and demonstrated that these systems were excellent tools to study virus replication in cell culture. In this study, we first performed DNA microarray analysis of the replicon-bearing cells to identify cellular factors associated with NV replication. The analysis demonstrated that genes in lipid (cholesterol) or carbohydrate metabolic pathways were significantly (p< 0.001) changed by the gene ontology analysis. Among genes in the cholesterol pathways, we found that mRNA levels of hydroxymethylglutaryl-CoA (HMG-CoA) synthase, squalene epoxidase and acyl-CoA:cholesterol acyltransferase(ACAT) 1, ACAT 2, small heterodimer partner, and low density lipoprotein receptor (LDLR)-related proteins were significantly changed in the cells.

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