Hepatitis C virus genotype 1b chimeric replicon containing genotype 3 NS5A domain

Robert E. Lanford, Bernadette Guerra, Helen Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Infections with hepatitis C virus (HCV) genotype 3 exhibit differences in clinical phenotype including an increase in response to interferon therapy and development of steatosis. To initiate studies on genotype 3, we created a chimeric genotype 1b replicon containing a genotype 3a NS5A domain. The chimera was capable of efficient colony formation after the selection of a novel dominant adaptive mutation. Thus, domains from highly different strains can interact to form a functional replicase. A new genotype 1a replicon was constructed as well. Genotype specific influence on interferon sensitivity was examined using genotype 1a, 1b and chimeric 1b-3a replicons. The genotype 3a NS5A domain did not increase the sensitivity of the chimeric replicon to IFNα. The results suggest that NS5A is not sufficient to convey the increased IFNα response by genotype 3 or the replicon model is not capable of mimicking the events involved in increased sustained viral response.

Original languageEnglish (US)
Pages (from-to)192-202
Number of pages11
JournalVirology
Volume355
Issue number2
DOIs
StatePublished - Nov 25 2006
Externally publishedYes

Keywords

  • HCV
  • IFNα
  • ISG
  • Interferon stimulated genes

ASJC Scopus subject areas

  • Virology

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