Prevalence of NS3 Mutations Inducing Resistance to Protease Inhibitors in Chronically Infected Hepatitis C Virus Genotype 4 Patients in Egypt
Ahmed Gaballah *
Department of Microbiology, Medical Research Institute, Alexandria University, Egypt.
Iman Naga
Department of Microbiology, Medical Research Institute, Alexandria University, Egypt.
Amel Elsheredy
Department of Microbiology, Medical Research Institute, Alexandria University, Egypt.
Gamal Elsawaf
Department of Microbiology, Medical Research Institute, Alexandria University, Egypt.
Ola Kader
Department of Microbiology, Medical Research Institute, Alexandria University, Egypt.
*Author to whom correspondence should be addressed.
Abstract
Background and Objectives: Directly acting antiviral agents, like NS3 protease inhibitors, are representing the backbone for the current therapy of Hepatitis C virus infection.
Given the heterogeneities in HCV genome, not all protease inhibitors will be equally effective against all HCV genotypes and subtypes. Data on HCV-4 mainly Egyptian strains are still inadequate.
Here we investigated the prevalence of natural NS3 mutations and Resistance-associated substitutions (RAS) among HCV-4 Egyptian isolates.
Methods: The NS5b and NS3 domains from 40 HCV Egyptian patients (20 therapy-naïve and 20 pegylated interferon-experienced patients, who failed to achieve sustained viral response) were sequenced.
Results: Using NS5b nucleotide sequences, our 40 cases were genotyped as HCV-4 of which 38 (95%) were HCV-4a, and 2 (5%) were HCV-4o.
NS3 amino acid sequence analysis showed that substitutions C16T and V36L were detected in all cases while D168H/E and T54A were found in only 3 and 1 cases, respectively. No difference could be detected between naïve and experienced patients in NS3 polymorphism.
Conclusion: Our results confirm the high genetic diversity of NS3 in HCV-4 that could impair the use of some protease inhibitors to treat HCV-4 infections. The use of cocktail therapy for HCV-4 is indispensable.
Keywords: Directly acting antiviral agents DAAs, protease inhibitors, NS3 polymorphism, resistance associated variants