title: High levels of HCV core+1 antibodies in HCV patients with hepatocellular carcinoma.
abstract: The core region of the hepatitis C virus (HCV) genome possesses an overlapping ORF that has been shown to encode a protein, known as the alternate reading frame protein (ARFP), F or core+1. The biological role of this protein remains elusive, as it appears to be non-essential for virus replication. However, a number of independent studies have shown that the ARFP/F/core+1 protein elicits humoral and cellular immune responses in HCV-infected individuals and interacts with important cellular proteins. To assess the significance of the core+1 humoral response in HCV-infected patients, we examined the prevalence of anti-core+1 antibodies in sera from patients with hepatocellular carcinoma (HCC) in comparison with chronically HCV-infected individuals without HCC. We produced two HCV core+1 histidine-tagged recombinant proteins for genotypes 1a (aa 11-160) and 1b (aa 11-144), as well as a non-tagged highly purified recombinant core+1/S protein (aa 85-144) of HCV-1b. Using an in-house ELISA, we tested the prevalence of core+1 antibodies in 45 patients with HCC in comparison with 47 chronically HCV-infected patients without HCC and 77 negative-control sera. More than 50 % of the serum samples from HCC patients reacted with all core+1 antigens, whereas <26 % of the sera from the non-HCC HCV-infected individuals tested positive. No core+1-specific reactivity was detected in any of the control samples. In conclusion, the high occurrence of anti-core+1 antibodies in the serum of HCC patients suggests a role for the ARFP/F/core+1 protein in the pathogenesis of HCC.
authors.affiliation: Democritus University of Thrace Medical School, Alexandroupolis, Greece.|Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Dalagiorgou
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Vassilaki
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Foka
authors.affiliation: University of Strasbourg-CNRS FRE 3211, Oncoprotein group, IREBS, Illkirch, France.|Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Boumlic
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Kakkanas
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kochlios
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Khalili
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Aslanoglou
authors.affiliation: Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Veletza
authors.affiliation: University of Strasbourg-CNRS FRE 3211, Oncoprotein group, IREBS, Illkirch, France.
authors.forename: G
authors.initials: G
authors.lastname: Orfanoudakis
authors.affiliation: Academic Department of Medicine, Athens University School of Medicine, Hippokration General Hospital, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Vassilopoulos
authors.affiliation: Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hadziyannis
authors.affiliation: Second Department of Internal Medicine, Medical School of Athens, Hippokration General Hospital, Athens, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Koskinas
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Mavromara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D018937:Hepatitis C Antibodies; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus