Hepatitis C virus core protein substitutions affect the response to pegylated-interferon and ribavirin therapy

BackgroundHepatitis C virus (HCV) shows remarkable genetic diver-sity, which contributes to its high persistence and variedsusceptibilities to antiviral treatments. Previous studieshave reported that the substitution of amino acids in theHCV-1b core region at positions 70 (Arg70 to Gln70)and/or 91 (Lue91 to Met91) is associated with a poorresponse to pegylated- interferon and ribavirin (PEG-IFN/RBV) therapy [1,2]. Because the role of the core protein inHCV infections is unclear in Saudi populations, we aimedin this study to analyze the full-length core proteinsequences from Saudi patients.Materials and methodsA total of 300 samples were obtained from Saudi patientswho went through PEG-IFN/RBV treatment. Sampleswere divided further to responder and non-respondergroups. Direct sequencing was employed, followed bysequence analyses using advanced software.ResultsOurdatashowedthattherewassignificantassociationbetween core protein mutations, particularly at position70, and treatment outcome in HCV1b and HCV-4d butnot in HCV-1a and HCV-4a clinical samples. In addition,amino acid residue at position 91 was well-conservedamong all clinical samples where Cys91 is the dominantamino acid residue. Furthermore, our data reported pointmutations at different positions that were flagged as ‘rare’mutations by negative BLOSUM scores.ConclusionsAmino acid substitution pattern differs substantiallyamong HCV sub-genotypes. Such discrepancy needsfurther investigations. Our finding provides a new insightinto HCV among effected Saudi population where theknowledge of HCV polymorphisms is lacking.