An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation.
OBJECTIVE
The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. Although clinical observations are consistent with a direct effect of HCV genotype 3a on lipid metabolism, experimental systems have focused on the expression of HCV proteins of genotype 1. To extend these observations, we established an in vitro model expressing the HCV core of different genotypes.


METHODS
The HCV core protein from patients with severe (genotype 3a) or no (genotypes 1b, 2a, 3h, 4h and 5a) liver steatosis was expressed in Huh7 cells. Core protein expression (by immunohistochemistry and immunoblot) and triglycerides accumulation (by Oil Red O stain and enzymatic measurement) were evaluated 48h after transfection.


RESULTS
Although triglyceride accumulation occurred with genotypes 1b, 3a and 3h, the genotype 3a core protein expression resulted in the highest level of accumulation (i.e. about 3-fold with respect to 1b, and 2-fold with respect to 3h). This effect was not related to core protein expression levels and was abolished by culturing cells in lipid-free medium.


CONCLUSIONS
Consistent with observations in chronic hepatitis C patients, the in vitro expression of HCV genotype 3a core protein is the ideal candidate model for studying the mechanisms of HCV-associated steatosis.
Abid
Karim
K
Division of Gastroenterology and Hepatology, University Hospital, 24 rue Micheli-du-Crest, CH-1211 Geneva, Switzerland.
Pazienza
Valerio
V
de Gottardi
Andrea
A
Rubbia-Brandt
Laura
L
Conne
Beatrice
B
Pugnale
Paolo
P
Rossi
Christine
C
Mangia
Alessandra
A
Negro
Francesco
F
D000328:Adult; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D016384:Consensus Sequence; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics
D014280:Triglycerides; D014758:Viral Core Proteins