Abstract
Hepatitis C virus (HCV), which is a major cause of liver diseases worldwide, undergoes genetic variation during the course of infection. The aim of this study was to examine sequence variations within the HVR1 region of HCV genotype 4 in infected Saudi patients treated with a combination therapy of interferon-α and ribavirin. cDNA of the HVR1 region of HVC-4 from one responder and one non-responder patients was generated, cloned and sequenced. Ten clones were randomly selected and analyzed for changes in nucleotide and amino acid sequences before the start of treatment, and subsequently three and six months after the start of the therapy course. Based on nucleotide and amino acid sequence variations, the HVR1 region is highly sequence variable. In both the responder and the non-responder patients, amino acid sequence variations were observed and a clear distinction between patients was evident. The amino acid changes after the treatment course were different in the responder compared to the non-responder subject. Five amino acids (residues 364 to 367, 381 and 409) were unique in the non-responder patient. Considerable amino acid variations were observed in the HVR1 region in both responder and non-responder patients. These findings could have implications for the development of an HCV vaccine as well as treatment protocols for HCV infections.
Highlights
Hepatitis C virus (HCV), which is a major cause of liver diseases worldwide, undergoes genetic variation during the course of infection
To examine the sequence variation of HCV genome during the course of treatment, hypervariable region 1 (HVR1) PCR product from a representative sample of patient who responded to the combination therapy were cloned before and three and six months after initiation of therapy
HVR1 amino acid changes Analysis of the frequency of variations at each codon position of HVR1 in all sixty clones has shown that variations at amino acids 364 to 467, 381 and 409 are unique to the non-responder patient (Figure 4). Viral factors such as genotype and pretreatment titer are known to influence the outcome of therapy of HCV infected patients with IFN–α [22,23]
Summary
Hepatitis C virus (HCV), which is a major cause of liver diseases worldwide, undergoes genetic variation during the course of infection. HCV exhibits great genetic variations during its course of infection, a biological phenomenon attributed to several reasons including the lack of a proof-reading mechanism of its RNA polymerase and the host immune pressure that could force the virus to undergo genetic changes allowing it to escape the killing power of host defenses [4]. Such genetic variability across the whole genome could reach 30% between all genotypes worldwide and 8-10% among subtypes of the same genotype [1]. The molecular mechanisms through which this resistant population is selected is not understood [10]
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