Hepatitis C virus genotype 1b chimeric replicon containing genotype 3 NS5A domain.
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 IFNalpha. The results suggest that NS5A is not sufficient to convey the increased IFNalpha response by genotype 3 or the replicon model is not capable of mimicking the events involved in increased sustained viral response.
Lanford
Robert E
RE
Department of Virology and Immunology, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227, USA. rlanford@icarus.sfbr.org
Guerra
Bernadette
B
Lee
Helen
H
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics; D011995:Recombination, Genetic; D012093:Replicon; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase