Infectious cDNA clone of the hepatitis C virus genotype 1 prototype sequence.
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.
Lanford
Robert E
RE
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.
Lee
Helen
H
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.
Chavez
Deborah
D
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.
Guerra
Bernadette
B
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.
Brasky
Kathleen M
KM
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.
D000818:Animals; D003001:Cloning, Molecular; D016384:Consensus Sequence / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D004274:DNA, Recombinant / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology; D006526:Hepatitis C / Q000821:virology; D009154:Mutation / Q000235:genetics; D002679:Pan troglodytes / Q000821:virology; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
D018076:DNA, Complementary; D004274:DNA, Recombinant; D012367:RNA, Viral