The influence of cholesterol and lipid metabolism on host cell structure and hepatitis C virus replication

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DOIResolve DOI: http://doi.org/10.1139/O05-149
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TypeArticle
Journal titleBiochem. Cell Biol.
Volume84
Issue1
Pages6779; # of pages: 13
AbstractThe hepatitis C virus (HCV) replicates on a membrane protein complex composed of viral proteins, replicating RNA, and altered cellular membranes. Small-molecule inhibitors of cellular lipid�cholesterol metabolism such as 25-hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 all show a negative effect on HCV replication. Perturbation of host cell lipid and cholesterol metabolism can disrupt replication complexes by altering membranous structures where replication occurs. Changes in cholesterol and (or) lipid composition can have a general effect on membrane structure. Alternatively, metabolic changes can exert a more subtle influence over replication complexes by altering localization of host proteins through alterations in lipid anchoring. Here, we use Huh-7 cells harboring subgenomic HCV replicons to demonstrate that 25-hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 do not disrupt the membranous web where replication occurs, whereas cholesterol-depleting agents such as ?-cyclodextrin do. Cellular imaging suggests that the HCV RNA can remain associated with subcellular compartments connected with replication complexes in the presence of metabolic inhibitors. Therefore, at least 2 different molecular mechanisms are possible for the inhibition of HCV replication through the modulation of cellular lipid and cholesterol metabolism.
Publication date
AffiliationNational Research Council Canada; NRC Steacie Institute for Molecular Sciences
Peer reviewedNo
NPARC number12337987
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Record identifier09473ed2-273a-43b0-acc0-0f327cc3f85f
Record created2009-09-10
Record modified2016-05-09
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