High levels of HCV core+1 antibodies in HCV patients with hepatocellular carcinoma Dalagiorgou, G. and Vassilaki, N. and Foka, P. and Boumlic, A. and Kakkanas, A. and Kochlios, E. and Khalili, S. and Aslanoglou, E. and Veletza, S. and Orfanoudakis, G. and Vassilopoulos, D. and Hadziyannis, S. J. and Koskinas, J. and Mavromara, P.,, 92, 1343-1351 (2011), doi = https://doi.org/10.1099/vir.0.023010-0, publicationName = Microbiology Society, issn = 0022-1317, 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., language=, type=