Dataset Information

Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.

ABSTRACT: BACKGROUND:Exploring the rate of naturally occurring NS3 protease mutants in HCV infected population is influential in the future therapeutic approaches. OBJECTIVES:This study explored naturally occurring resistant mutations to protease inhibitors in a pilot study. PATIENTS AND METHODS:We analyzed NS3 gene sequences in 7 HCV infected patients, referred to the central liver center, south of Iran. The protease domain was amplified by PCR followed by product extraction. Amplified NS3 genes were cloned by TA/cloning system. For each patient, clonal-sequencing was performed to improve mutation detection sensitivity. Then, the obtained sequences were compared with the reference sequences and final phylogenic tree was constructed. Afterwards, the sequences were studied to investigate point mutations. RESULTS:Phylogenetic analysis between reference and amplified sequences demonstrated high similarity of all sequences with genotype 1. Interestingly, crucial protease resistant mutations were detected in V36 and R155 positions in one patient's sequence. Checking different clones of this patient confirmed V36L, as the dominant mutation while R155K was detected only in a few cases. CONCLUSIONS:As revealed, naturally occurring resistant mutations, especially R155K in protease sequence were identified in 1 out of the 7 patients, so the rate of such mutations is estimated to be high. It seems that checking HCV patients before protease inhibitor treatment are necessary in the region.

SUBMITTER: Afrasiabi M

PROVIDER: S-EPMC4644313 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.

Afrasiabi Mozhgan M Hosseini Seyed Younes SY Yaghobi Ramin R Fattahi Mohammad-Reza MR Ardebili Maryam M Khodadad Mahboobeh M

Jundishapur journal of microbiology 20151029 10

<h4>Background</h4>Exploring the rate of naturally occurring NS3 protease mutants in HCV infected population is influential in the future therapeutic approaches.<h4>Objectives</h4>This study explored naturally occurring resistant mutations to protease inhibitors in a pilot study.<h4>Patients and methods</h4>We analyzed NS3 gene sequences in 7 HCV infected patients, referred to the central liver center, south of Iran. The protease domain was amplified by PCR followed by product extraction. Amplif ...[more]

PMID: 26587218

Similar Datasets

Project description:Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication-competent, drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multidrug resistance. Collectively, however, 8.6% of the patients infected with genotype 1a and 1.4% of those infected with genotype 1b carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses in vivo.Naturally occurring dominant STAT-C resistance mutations are common in treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin.

Dataset Information

Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.

Publications

Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets