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Journal of General Virology (2001), 82, 1291-1297.
© 2001 Society for General Microbiology

Animal: RNA Viruses

Infectious cDNA clone of the hepatitis C virus genotype 1 prototype sequence

Robert E. Lanford1, Helen Lee1, Deborah Chavez1, Bernadette Guerra1 and Kathleen M. Brasky2

Department of Virology and Immunology1 and Department of Laboratory Animal Medicine2, Southwest Regional Primate Research Center, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227, USA

Author for correspondence: Robert Lanford. Fax +1 210 670 3329. e-mail rlanford{at}icarus.sfbr.org

A full-length cDNA clone of the hepatitis C virus (HCV) genotype 1 prototype (subtype 1a) sequence was constructed. Synthetic RNA produced from the initial cDNA clone was not infectious following intrahepatic inoculation of a chimpanzee. A consensus clone was prepared by comparison with multiple full-length HCV sequences of genotypes 1, 2 and 3. A total of 11 non-consensus amino acid residues were altered by mutagenesis. Synthetic RNA from the repaired clone initiated a typical, acute-resolving HCV infection following intrahepatic inoculation of a chimpanzee. In addition, at least one of three chimeric cDNA clones constructed between the HCV-1 and H77 genotype 1a strains of HCV was infectious in a chimpanzee. This is the first example of an infectious chimeric HCV clone. An infectious cDNA clone of HCV-1 will be of particular value, since it is the prototype HCV sequence and many commonly used reagents are based on this sequence.




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