Activation of the interferon-inducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein.
Hepatitis C virus (HCV) is a major etiological agent of chronic liver disease and hepatocellular carcinoma (HCC). We demonstrate herewith that HCV core proteins encoded by sequences isolated from HCC tumor tissues, but not those derived from their non-tumor counterparts in the same liver, co-localise in vitro and in vivo and co-immunoprecipitate with PKR in hepatocytic Huh7 cells. We show that this association in fact augments the autophosphorylation of PKR and the phosphorylation of the translation initiation factor eIF2alpha, which are two markers of PKR activity. The present study therefore identifies a novel model of virus-cell interactions whereby a viral protein, the HCV core, activates PKR activity.
Delhem
N
N
Department of Liver Cancer and Molecular Virology, Unité INSERM U370, CHU Necker, 156 rue de Vaugirard, 75015 Paris, France.
Sabile
A
A
Gajardo
R
R
Podevin
P
P
Abadie
A
A
Blaton
M A
MA
Kremsdorf
D
D
Beretta
L
L
Brechot
C
C
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000821:virology; D004789:Enzyme Activation; D016174:Hepacivirus / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D016415:Sequence Alignment; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
D009363:Neoplasm Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D019892:eIF-2 Kinase