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

A full-length cDNA clone of tile hepatitis C virus (HCV) genotype 1 prototy pe (subtype 1 a) 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 f ull-length HCV sequences of genotypes 1, 2 and 3. A total of 11 non-consens us 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 thr ee chimeric cDNA clones constructed between the HCV-1 and H77 genotype la s trains 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 commo nly used reagents are based on this sequence.