Domain 3 of hepatitis C virus core protein is sufficient for intracellular lipid accumulation

Ravi Jhaveri*, Guan Qiang, Anna Mae Diehl

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 isolates of HCV genotype 3 core steatosis-associated d3 (d3S), non-steatosis-associated d3 (d3NS), and genotype 1 d3 (d3G1) were analyzed by means of immunofluorescence, oil red O (ORO) staining, and triglyceride quantitation. Results: Cells that expressed d3S had statistically significantly more ORO than did cells expressing d3NS or d3G1 (P=.02 and <.001, respectively), as well as higher triglyceride levels (Pp.03 and .003, respectively). Immunofluorescence analysis showed that d3 does not colocalize to lipid droplets but partially colocalizes to the Golgi apparatus. Conclusions: Our results suggest that HCV core d3 is sufficient to mediate the accumulation of lipid by means of a mechanism that is independent of domains 1 and 2. Our results also suggest that altered lipid trafficking may be involved.

Original languageEnglish (US)
Pages (from-to)1781-1788
Number of pages8
JournalJournal of Infectious Diseases
Volume200
Issue number11
DOIs
StatePublished - Nov 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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