Efficient cell culture system for hepatitis C virus genotype 6A

A nucleic acid molecule comprising a nucleic acid which encodes a recombinant human hepatitis C virus of genotype 6a/JFH1 that is capable of expressing said virus when transfected into cells, wherein said molecule encodes the amino acid sequence with a sequence identity of at least 95% to that of SEQ ID NO:

• 2, wherein said molecule comprises a T1389C adaptive mutation in the E1 gene and a T1581C, T1581G, or A1586G adaptive mutation in the E2 gene of SEQ ID NO:1, and wherein said adaptive mutations provide an improved ability to generate infectious viral particles in cell culture compared to an HCV genotype 6a/JFH1 virus without said adaptive mutations.

A method for producing a hepatitis C virus particle, comprising:

• (a) culturing a cell comprising a nucleic acid molecule which encodes human hepatitis C virus of genotype 6a/JFH1 that is capable of expressing said virus when transfected into cells and wherein said nucleic acid molecule encodes an amino acid sequence with a sequence identity of at least 95% to that of SEQ ID NO:2, wherein said molecule encodes adaptive mutations F350S in the E1 protein and T416A or N417T in the E2 protein of SEQ ID NO:2, said adaptive mutations providing an improved ability to generate infectious viral particles in cell culture compared to an HCV genotype 6a/JFH1 virus without said adaptive mutations;
• and,
• (b) allowing the cell to produce the virus.

A hepatitis C virus particle comprising a nucleic acid molecule which encodes human hepatitis C virus of genotype 6a/JFH1 that is capable of expressing said virus when transfected into cells and wherein said nucleic acid molecule encodes the amino acid sequence with a sequence identity of at least 95% to that of SEQ ID NO:2, wherein said molecule encodes adaptive mutations F350S in the E1 protein and a T416A or a N417T in the E2 protein of SEQ ID NO:2, and wherein said adaptive mutation provides an improved ability to generate infectious viral particles in cell culture compared to an HCV genotype 6a/JFH1 virus without said adaptive mutations.

A hepatitis C virus particle, comprising a nucleic acid which encodes a recombinant human hepatitis C virus of genotype 6a/JFH1 that is capable of expressing said virus when transfected into cells and wherein said nucleic acid encodes the amino acid sequence with a sequence identity of at least 95% to that of SEQ ID NO 2, wherein said molecule comprises a T1389C adaptive mutation in the E1 gene and a T1581C, T1581G, or A1586G adaptive mutation in the E2 gene of SEQ ID NO:1, and wherein said adaptive mutations provide an improved ability to generate infectious viral particles in cell culture compared to an HCV genotype 6a/JFH1 virus without said adaptive mutations.