Prevalence of hepatitis C virus-resistant association substitutions to direct-acting antiviral agents in treatment-naïve hepatitis C genotype 1b-infected patients in western China
| Autor: | Hu Li, Zhiwei Chen, Hong Ren, Peng Hu, Zhao Li |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
hepatitis C virus direct-acting antiviral agents Hepatitis C virus viruses 030106 microbiology resistance-associated substitutions medicine.disease_cause Therapy naive 03 medical and health sciences chemistry.chemical_compound Genotype 1b Genotype medicine Pharmacology (medical) NS5A NS5B Original Research Pharmacology NS3 business.industry virus diseases Hepatitis C biochemical phenomena metabolism and nutrition medicine.disease Virology digestive system diseases Infectious Diseases chemistry Infection and Drug Resistance business unstructured proteins |
| Zdroj: | Infection and Drug Resistance |
| ISSN: | 1178-6973 |
| Popis: | Zhao Li,*Zhi-wei Chen,*Hu Li,Hong Ren,Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work. Background: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) are potent and highly efficacious. However, resistance-associated substitutions (RASs) relevant to DAAs can impair treatment effectiveness even at baseline. Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in western China is still unclear. Materials and methods: Direct sequencing of the HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70 DAAs treatment-naïve HCV 1b-infected patients in western China. The sequences were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and amino-acid covariance patterns in the NS3, NS5A, and NS5B genes were analyzed by MEGA and Cytoscape (version 3.2.1), respectively.Results: The presence of at least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I, V170I) was observed in 85.48% (53 of 62) of patients, RASs in the NS5A region (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H) were observed in 42.42% (28 of 66) of patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I, M414L, I424V, A442T, V499A, S556G) were observed in 100% (44 of 44) of patients. Evolutionary patterns of RASs and amino-acid covariance patterns for the NS3, NS5A, and NS5B genes are reported.Conclusion: The prevalence of RASs relevant to DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment-naïve patients is high. Therefore, more attention should be paid to RASs associated with DAAs in the upcoming DAA-treatment era in China. Keywords: hepatitis C virus, unstructured proteins, resistance-associated substitutions, direct-acting antiviral agents. |
| Databáze: | OpenAIRE |
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