Patent ID: 8026092

Claim:
An isolated polynucleotide encoding a replication competent hepatitis C virus genotype 1a replicon comprising: a 5′ non-translated region (NTR), a 3′ NTR, and a first coding sequence present between the 5′ NTR and 3′ NTR and encoding a hepatitis C virus polyprotein, wherein the polyprotein comprises an amino acid sequence having at least about 95% identity to amino acids 1-3011 of SEQ ID NO:2, and wherein the amino acid sequence of the polyprotein comprises at least three adaptive mutations relative to the amino acid positions using SEQ ID NO: 2 as a reference sequence, wherein the adaptive mutations comprise an isoleucine at about amino acid 2204 of the polyprotein and at least two adaptive mutations selected from the group of an arginine at about amino acid 1067 of the polyprotein, an arginine at about amino acid 1691 of the polyprotein, a valine at about amino acid 2080 of the polyprotein, an isoleucine at about amino acid 1655 of the polyprotein, an arginine at about amino acid 2040 of the polyprotein, an arginine at about amino acid 1188 of the polyprotein, and a combination thereof.