DMCA
Domain 3 of Hepatitis C Core Protein is Sufficient for Intracellular Lipid Accumulation
BibTeX
@MISC{Jhaveri_domain3,
author = {Ravi Jhaveri and Guan Qiang and Anna Mae Diehl},
title = {Domain 3 of Hepatitis C Core Protein is Sufficient for Intracellular Lipid Accumulation},
year = {}
}
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Abstract
Background—Hepatitis C virus (HCV) is a major cause of liver disease worldwide with steatosis, or “fatty liver”, being a frequent histologic finding. In previous work, we identified sequence polymorphisms within domain 3 (d3) of genotype 3 HCV Core protein that correlated with steatosis and in vitro lipid accumulation. In this study, we investigated the sufficiency of d3 to promote lipid accumulation, the role of HCV genotype in d3 lipid accumulation and the subcellular distribution of d3. Methods—Stable cell lines expressing green fluorescent protein (GFP) fusions with HCV Core d3 from genotype 3 steatosis (d3S), non-steatosis (d3NS) and genotype 1 (d3G1) isolates were analyzed by immunofluorescence (IF), Oil Red O (ORO) staining and triglyceride (TG) quantitation Results—Cells expressing d3S had significantly more ORO than d3NS or d3G1 cells (p values: 0.02 and <0.0001 respectively) as well as TG (p=0.03 and 0.003 respectively). IF analysis showed domain 3 does not co-localize to lipid droplets but partially co-localizes to the Golgi. Conclusions—Our results suggest that HCV Core d3 is sufficient to mediate the accumulation of lipid by a mechanism that is independent of domains 1 and 2. Our results also suggest that altered lipid trafficking may be involved.
Keyphrases
intracellular lipid accumulation hepatitis core protein hcv core d3 liver disease worldwide hcv genotype oil red quantitation result cell d3 lipid accumulation subcellular distribution method stable cell line green fluorescent protein previous work background hepatitis virus lipid accumulation sequence polymorphism lipid droplet frequent histologic lipid trafficking vitro lipid accumulation hcv core protein d3g1 cell major cause
