Naturally occurring NS5B variants resistant to non-nucleoside or nucleoside polymerase inhibitors among treatment-naïve hepatitis C patients in south China

Abstract

To determine the prevalence of mutations in the non-structural protein 5B (NS5B) of the hepatitis C virus (HCV),which are associated with natural resistance to non-nucleoside and nucleoside polymerase inhibitors (PIs),in treatment-naive hepatitis C patients in south China. A nested PCR protocol that amplified three different regions of NS5B was used to detect the naturally occurring drag-resistant substitutions.Direct PCR sequencing was performed to analyze the sequences. NS5B mutations known to confer resistance to nucleoside PIs,such as A15G,S96T and S282T,were mainly detected in HCV genotype 6a (20/88,22.73%).Of the NS5B mutations known to confer resistance to non-nucleoside PIs,C316N and S365A were detected in HCV genotype lb (60/60,100% and 2/60,3.33%, respectively) and I482L and V499A were mainly detected in HCV genotype 2a (9/9,100% and 4/4,100%, respectively) and HCV genotype 6a (9/9,100% and 4/4,100%, respectively).Other NS5B mutations found in the study population included A1 5S,S365F,S365P,S368A and S368L;although none of these has been previously shown to confer resistance to PIs. Naturally occurring dominant PI resistance mutations in NS5B exist in treatment-na(i)ve hepatitis C patients in south China and may be related to the virus genotype.