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Characterization of Naturally Occurring NS5A and NS5B Polymorphisms in Patients Infected with HCV Genotype 3a Treated with Direct-Acting Antiviral Agents.
- Source :
-
Viruses [Viruses] 2017 Aug 07; Vol. 9 (8). Date of Electronic Publication: 2017 Aug 07. - Publication Year :
- 2017
-
Abstract
- Hepatitis C virus (HCV) genotype (GT)3 is associated with increased risk of steatosis, development of cirrhosis and hepatocellular carcinoma. Limited data are available regarding genetic variability and use of direct-acting antiviral agents in these patients. non-structural protein 5A (NS5A) and non-structural protein 5B (NS5B) sequencing was performed on 45 HCV GT3-infected Italian patients subsequently treated with sofosbuvir ± daclatasvir (SOF ± DCV). Novel GT3a polymorphisms were observed by Sanger sequencing in three NS5A (T79S, T107K, and T107S) and three NS5B (G166R, Q180K, and C274W) baseline sequences in patients who achieved sustained virological response (SVR). Baseline NS5A resistance-associated substitutions A30K and Y93H were detected in 9.5% of patients; one patient with A30K did not achieve SVR. Phylogenetic analyses of sequences showed no distinct clustering. Genetic heterogeneity of NS5A and NS5B was evaluated using ultra-deep pyrosequencing (UDPS) in samples longitudinally collected in patients not achieving SVR. Some novel NS5A and NS5B polymorphisms detected at baseline may not impact treatment outcome, as they were not enriched in post-failure samples. In contrast, the novel L31F NS5A variant emerged in one treatment failure, and I184T, G188D and N310S, located on the same NS5B haplotype, became predominant after failure. These findings suggest a potential impact of these novel substitutions on the treatment outcome; however, their significance requires further investigation.<br />Competing Interests: B. Bartolini, E. Giombini, C. Taibi, R. Lionetti, M. Montalbano, U. Visco-Comandini, G. D’Offizi, M.R. Capobianchi, and A.R. Garbuglia declare no conflict of interest. F. McPhee is an employee of Bristol Myers Squibb.
- Subjects :
- Adult
Aged
Antiviral Agents
Drug Resistance, Viral
Drug Therapy, Combination
Female
Genetic Variation
Genotype
Hepatitis C, Chronic blood
Hepatitis C, Chronic epidemiology
Hepatitis C, Chronic virology
High-Throughput Nucleotide Sequencing
Humans
Italy epidemiology
Male
Middle Aged
Phylogeny
Treatment Failure
Treatment Outcome
Hepacivirus drug effects
Hepacivirus genetics
Hepatitis C, Chronic drug therapy
Polymorphism, Genetic
Viral Nonstructural Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 9
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 28783119
- Full Text :
- https://doi.org/10.3390/v9080212