The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism

Ya Hui Tsai, Wan Fen Kuang, Tsai Yi Lu, Jia Horng Kao, Ming Yang Lai, Chun Jen Liu, Pei Jer Chen, Lih Hwa Hwang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Background/Aims: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 usually respond better to interferon (IFN) treatment than those infected with genotype 1. In this study, we investigated whether the non-structural 5A protein (NS5A) of HCV genotypes 1 and 2 (1b-NS5A and 2a-NS5A, respectively) exerted differential counteractivities against IFN treatment. Methods: We compared the inhibitory effects of 1b-NS5As and 2a-NS5As on IFN activity. We also investigated the replication inhibition of HCV subgenomic replicons containing 1b-NS5A or 2a-NS5A in response to IFN treatment. Results: 1b-NS5As exerted more profound inhibitory effects on IFN activity than 2a-NS5As. The replication of the 2a-NS5A-containing replicons was more sensitive to IFN treatment than that of the 1b-NS5A-containing replicons. Deletion of the interferon sensitivity-determining region/protein kinase R-binding domain (PKR-BD), the V3 domain, or the C-terminus region of NS5A significantly abrogated its anti-IFN activity. Domain swapping between 1b-NS5A and 2a-NS5A in the V3 domain and/or the C-terminus region resulted in a transfer of their anti-IFN activity. Conclusions: 1b-NS5As exert higher magnitudes of IFN antagonism than do 2a-NS5As. The V3 and the C-terminus regions are responsible for the differential anti-IFN effects. This phenomenon may partly explain the genotype-linked differences in the response of HCV to IFN treatment.

Original languageEnglish
Pages (from-to)899-907
Number of pages9
JournalJournal of Hepatology
Issue number6
StatePublished - Dec 2008


  • Genotype
  • Hepatitis C virus
  • IFN antagonism
  • NS5A


Dive into the research topics of 'The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism'. Together they form a unique fingerprint.

Cite this