Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates.
Several lines of evidence suggest that hepatitis C virus (HCV) core protein may modulate cellular transduction signals and alter lipid metabolism. We have investigated the binding of HCV core protein to cellular proteins by combining 2 yeast hybrid, confocal, and surface plasmon resonance assays. Our results show the direct binding of the viral protein to apolipoprotein AII (apoAII) and map the interaction domain to the C-terminal of HCV core protein. To investigate the biological relevance of the interaction between HCV core and lipid metabolism, we took advantage of the well-established increase in apoAII expression caused by fibrates in HepG2 cells. After fenofibric acid treatment, we show a parallel increase in apoAII and core protein secretion, this effect being abolished by brefeldin A. Our study identifies apoAII as one of the cellular targets for HCV core protein. We also show that the intervention of fenofibric acid in cellular lipid metabolism directly affects the expression pattern of HCV core protein.
Sabile
A
A
Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Perlemuter
G
G
Bono
F
F
Kohara
K
K
Demaugre
F
F
Kohara
M
M
Matsuura
Y
Y
Miyamura
T
T
Bréchot
C
C
Barba
G
G
D016633:Apolipoprotein A-II / Q000235:genetics / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D003470:Culture Media / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
D016633:Apolipoprotein A-II; D003470:Culture Media; D018076:DNA, Complementary; D000960:Hypolipidemic Agents; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D020126:Brefeldin A; C006012:fenofibric acid; D011345:Fenofibrate