Genetic Diversity of Hepatitis C Virus Genotype 3a Based on Complete Core Protein in Peshawar, Pakistan

Abstract

Background: Hepatitis C virus (HCV) belongs to the genus Hepacivirus and family Flaviviridae and is a leading cause of chronic liver diseases including cirrhosis and hepatocellular carcinoma. Objectives: This study aimed to analyze the genetic diversity of HCV genotype 3a based on complete core protein in Peshawar. Methods: Hepatitis C virus genotype 3a infected patients, belonging to different areas of Peshawar participated in this study. The complete core gene of HCV 3a was amplified and sequenced. The obtained sequences were used for mutational and phylogenetic analysis using CLUSTAL W and MEGA 6 software. Results: Phylogenetic analysis revealed that most of the HCV 3a strains prevalent in Peshawar are genetically closer to HCV 3a strains previously reported from Pakistan and India. Analysis of translated amino acids aligned against reference 3a strain (NZL1) demonstrated substitutions in three functional domains (D1, D2, D3) of the core protein. Core protein mutations R70Q (arginine to glutamine) and L/C91M (leucine/cysteine to methionine) were not found among studied isolates. In sequence PK/59 at position 72, glutamic acid was replaced with aspartic acid. Position 182 was occupied by leucine in place of phenylalanine in all sequences. Alanine and serine amino acids at the positions of 189 and 191 were replaced with threonine and cysteine, respectively. In seven of our isolates (PK/59-PK/68) glutamic acid and serine were found mutated to aspartic acid and cysteine, respectively. Conclusions: HCV core protein, although a conserved region could be considered a phylogenetic marker for the determination of genetic relatedness among circulating viral strains and tracing the outbreak of an infection. Geographical, regional, and genotypic differences are effective in the prevalence of substitutions in HCV core protein.