The Relationship Between HCV-NS۵A Gene Mutations and Resistance to Combination Therapy in Patients with HCV- Genotype ۱-B

Background: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease, as it holds a significant role in developing liver cirrhosis and hepatocellular carcinoma. Combination therapy with Pegaferon and Ribavirin leads to viral clearance of only ۵۰% of patients. During the host antiviral response, protein kinase R (PKR) interacts with eukaryotic translation initiation factor ۲ alpha (eIF۲α), that leads to the inhibition of viral protein synthesis. The viral NS۵A protein appears to interfere with this antiviral action, evading the host immune response. However, mutations in the NS۵A gene have been observed to render HCV more susceptible to treatment. The aim of this study was to determine the mutations present in the IFN Sensitivity Determining Region (ISDR) and NS۵A-PKRbinding domain regions in chronic HCV infected patients before and after therapy. Methods: Viral RNA was isolated from the plasma of ۵۲ chronic HCV infected patients before and after treatment. RT-Nested PCR reaction was used to reverse transcription and amplification of target fragment using the specific primers. Results: Sequence analysis revealed no relationship between NS۵A mutations and response to treatment. No significant difference was found between the mutations before and ۳ months after treatment among responders and non-responders. Conclusions: This study showed that the number of mutations in NS۵A did not significantly differ between the patients who responded to treatment and the patients that did not. Therefore, sequencing of these regions does not appear to be a suitable tool for predicting treatment outcomes.

Keywords:

Genotype b۱ , Hepatitis C virus , Mutation , Non-structural protein (NS۵A) , Response to combination therapy