Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures

Journal of Viral Hepatitis
Y JeongSeungtaek Kim

Abstract

Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this ...Continue Reading

References

Nov 20, 2002·Journal of Virology·Keril J BlightCharles M Rice
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·MinKyung YiStanley M Lemon
Aug 28, 2007·Nature Cell Biology·Yusuke MiyanariKunitada Shimotohno
Mar 29, 2008·PLoS Pathogens·Timothy L TellinghuisenJason Treadaway
Apr 29, 2011·Journal of Virology·Seungtaek KimStanley M Lemon
Mar 19, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fiona McPheeDavid Gardiner
Jul 30, 2014·Nature Medicine·Daisuke YamaneStanley M Lemon
Jan 8, 2015·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Jun ItakuraNamiki Izumi
Jun 23, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Erik LontokVeronica Miller
Apr 6, 2016·Clinical and Molecular Hepatology·UNKNOWN Korean Association for the Study of the Liver
Oct 28, 2016·Gut and Liver·Seungtaek KimSang Hoon Ahn

❮ Previous
Next ❯

Citations

May 3, 2019·Clinical and Molecular Hepatology·Tommaso Lorenzo ParigiAlessio Aghemo
Nov 22, 2020·Journal of Hepatology·Julia DietzUNKNOWN Members of the German HCV resistance study group

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.