TY - JOUR
T1 - Domain 3 of hepatitis C virus core protein is sufficient for intracellular lipid accumulation
AU - Jhaveri, Ravi
AU - Qiang, Guan
AU - Diehl, Anna Mae
N1 - Funding Information:
Financial support: National Institutes of Health (grant K08DK76598 to R.J.); American Liver Foundation and American Association for the Study of Liver Diseases (Sheila Sherlock Translational Research Award to R.J.); Duke Children’s Miracle Network (grant to R.J.); Duke Center for AIDS Research.
PY - 2009/11/1
Y1 - 2009/11/1
N2 - 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.
AB - 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.
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U2 - 10.1086/648094
DO - 10.1086/648094
M3 - Article
C2 - 19852667
AN - SCOPUS:72849151027
SN - 0022-1899
VL - 200
SP - 1781
EP - 1788
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -
