Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation.
BACKGROUND
Steatosis is a common histological finding and a poor prognostic indicator in patients with hepatitis C virus (HCV) infection. In HCV genotype 3-infected patients, the etiology of steatosis appears to be closely correlated with unknown viral factors that increase intracellular lipid levels. We hypothesize that specific sequence polymorphisms in HCV genotype 3 core protein may be associated with hepatic intracellular lipid accumulation.


METHODS
Using selected serum samples from 8 HCV genotype 3-infected patients with or without steatosis, we sequenced the HCV core gene to identify candidate polymorphisms associated with increased intracellular lipid levels.


RESULTS
Two polymorphisms at positions 182 and 186 of the core protein correlated with the presence (P= .03) and absence (P= .005) of intrahepatic steatosis. Transfected liver cell lines expressing core protein with steatosis-associated polymorphisms had increased intracellular lipid levels compared with non-steatosis-associated core isolates, as measured by oil red O staining (P= .02). Site-specific mutagenesis performed at positions 182 and 186 in steatosis-associated core genes yielded proteins that had decreased intracellular lipid levels in transfected cells (P= .03).


CONCLUSIONS
We have identified polymorphisms in HCV core protein genotype 3 that produce increased intracellular lipid levels and thus may play a significant role in lipid metabolism or trafficking, contributing to steatosis.
Jhaveri
Ravi
R
Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. ravi.jhaveri@duke.edu
McHutchison
John
J
Patel
Keyur
K
Qiang
Guan
G
Diehl
Anna Mae
AM
D000328:Adult; D000595:Amino Acid Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014758:Viral Core Proteins / Q000235:genetics*
D014758:Viral Core Proteins