Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection.

Heidar Sharafi,Pooneh Rahimi,Golnaz Bahramali,Nafiseh Sadat Asadi,Seyed Moayed Alavian,Seyedeh Zahra Moravej,FaridehSadat SajadianFard,Vahid Iranpur Mobarakeh

doi:10.3389/fmicb.2020.617375

Heidar Sharafi, Pooneh Rahimi + Show 6 more

Open Access

https://doi.org/10.3389/fmicb.2020.617375

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Abstract

BackgroundHepatitis C virus (HCV), non-structural 5A (NS5A), and non-structural 5B (NS5B) resistance-associated substitutions (RASs) are the main causes of failure to direct-acting antiviral agents (DAAs). NS5A and NS5B RASs can occur in patients with HCV infection naturally and before exposure to DAAs.ObjectivesThis study aimed to evaluate naturally-occurring NS5A and NS5B RASs in Iranian patients with HCV genotype 1a (HCV-1a) and -3a infections.MethodsIn this cross-sectional study, viral RNA was extracted from serum specimens. NS5A and NS5B regions were amplified using RT-PCR followed by DNA sequencing. The results of nucleotide sequences were aligned against reference sequences of HCV-1a and -3a and the amino acid substitutions were analyzed using geno2pheno [hcv] web application.ResultsAmong 135 patients with hepatitis C, NS5A amino acid substitutions/RASs were identified in 26.4% and 15.9% of patients with HCV-1a and -3a infections, respectively. The identified amino acid substitutions/RASs in the NS5A region of patients with HCV-1a infection were M28T/V/I 11.1%, Q30R/H 4.2%, L31M 1.4%, and H58Y/P/C/D/Q/S/T 16.7%. Y93H substitution was not found in HCV-1a sequences. In patients with HCV-3a infection, NS5A amino acid substitutions/RASs were A30T/K 9.5%, L31F 1.6%, P58S/T/C 3.2%, Y93H 3.2%, and Y93N 3.2%. No resistance substitutions were identified in NS5B sequences from patients with HCV-1a and -3a infections.ConclusionIn this study, baseline amino acid substitutions/RASs were only identified in the NS5A region in Iranian patients with HCV-1a and -3a infections, and the prevalence of these amino acid substitutions/RASs were in accordance with similar studies. There were no RASs in the HCV-1a and -3a NS5B region.

Highlights

It has been estimated that approximately 71 million people worldwide are chronically infected with the hepatitis C virus (HCV)
Baseline Characteristics of Study Population. Both target regions (NS5A and non-structural 5B (NS5B)) of HCV were successfully amplified in 72/72 and 63/63 patients who were infected with HCV genotype 1a (HCV-1a) and -3a, respectively
All patients were direct-acting antiviral agents (DAAs)-naïve, 44.4% of patients with HCV-1a and 30.2% of patients with HCV-3a had a previous history of IFN-based treatment

Summary

Introduction

It has been estimated that approximately 71 million people worldwide are chronically infected with the hepatitis C virus (HCV). Viral RNA-dependent RNA polymerase of HCV which lacks 3 to 5 exonuclease proofreading activity leads to a high genome replication rate with no fidelity, and enables HCV to escape from selective pressures of the immune response and antiviral therapies (Kau et al, 2008; Paolucci et al, 2013; Murphy et al, 2015; de Rueda et al, 2017) All these characteristics make HCV a challenging target for designing effective vaccine and antiviral drugs (Murphy et al, 2007; Gottwein et al, 2009; Nakano et al, 2012; Smith et al, 2014; Walker et al, 2015; Alavian and Sharafi, 2017; de Rueda et al, 2017; Mahmud et al, 2018).

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