Full length HCV clones have been produced and shown to be infectious upon transfectin directly into chimpanzee livers. Two chimps were inoculated and both developed HCV infections and disease typical of HCV in chimpanzees following IV inoculation of infectious serum. Both these animals have become chronically infected. As both these animals were infected with clonal virus that was of a single uniform sequence, detailed analyses of the evolution of this virus was possible. It has been claimed that mutations in the hypervariable region of E2 result in escape mutants and allow the persistent infection. We have shown that mutations in the so called hypervariable region of the E2 envelope glycoprotein are not responsible for the maintenance of the persistent infections. Both animals developed anti HCV antibody including antibody to the two envelope glycoproteins , E1 and E2, and the HVR at the amino terminus of E2. The virus in both chimpanzees showed some variability over a one year period of observation. However, no changes were observed in the HVR of the viral genomes from either animal. A series of mutants have also been created in the infectious clone and tested for viability. As predicted none of them were viable. A second infectious clone representing genotype 1b virus has been prepared and will soon be tested in a chimpanzee.
