HIGH-YIELD GENOTYPE 1a, 2a AND 3a HCV

A method for producing a hepatitis C virus particle or a hepatitis C virus-like particle comprising culturing a cell or raising an animal to to produce either the virus or the hepatitis C virus-like particle, wherein the cell or animal comprises a nucleic acid molecule encoding a human hepatitis C virus or the hepatitis C virus like particle selected from:

• a hepatitis C virus derived from genotype 1a and said nucleic acid molecule encodes an amino acid sequence comprising one of the following groups of adaptive mutations:
• a) S2482G, N2651H, 12902L and H2986R according to SEQ ID NO:
• 25;
• or
• b) T2357A, S2375G, C2419R, M2834L and H2986R according to SEQ ID NO:
• 25;
• a hepatitis C virus derived from genotype 2a and said nucleic acid molecule encodes an amino acid sequence comprising the following adaptive mutations:
• K78E, V140L, T329S, H434N, A575T, A760T, V773A, V828A, A1146V, I1330V, L1500P, V1835I, T2000A, L2363P, A2367P, E2783Q and L3013S according to SEQ ID NO:
• 26;
• or
• a hepatitis C virus derived from genotype 3a and said nucleic acid molecule encodes an amino acid sequence comprising the following adaptive mutations:
• G395R, A856T, G875R, N1589S, 11753S, V2428A and D2807G according to SEQ ID NO:
• 27.

A method of treating, alleviating or preventing a hepatitis C virus infection, the method comprising administering to a subject a hepatitis C virus particle or a hepatitis C virus like particle comprising a nucleic acid sequence or a hepatitis C virus vaccine comprising the nucleic acid sequence or the encoded amino acid sequence thereof, wherein the nucleic acid molecule encoding the human hepatitis C virus or the hepatitis C virus like particle is selected from:

• a hepatitis C virus derived from genotype 1a and said nucleic acid molecule encodes an amino acid sequence comprising one of the following groups of adaptive mutations:
• a) S2482G, N2651H, 12902L and H2986R according to SEQ ID NO:
• 25;
• or
• b) T2357A, S2375G, C2419R, M2834L and H2986R according to SEQ ID NO:
• 25;
• a hepatitis C virus derived from genotype 2a and said nucleic acid molecule encodes an amino acid sequence comprising the following adaptive mutations:
• K78E, V140L, T329S, H434N, A575T, A760T, V773A, V828A, A1146V, I1330V, L1500P, V1835I, T2000A, L2363P, A2367P, E2783Q and L3013S according to SEQ ID NO:
• 26;
• or
• a hepatitis C virus derived from genotype 3a and said nucleic acid molecule encodes an amino acid sequence comprising the following adaptive mutations:
• G395R, A856T, G875R, N1589S, 11753S, V2428A and D2807G according to SEQ ID NO:
• 27.

A method for screening an anti-hepatitis C virus substance, comprising

• a) culturing a cell comprising a nucleic acid molecule, which replicates human hepatitis C virus or a hepatitis C virus like particle;
• and
• b) detecting the replicating RNA or the virus particles in the resulting culture
• wherein the nucleic acid molecule encodes a human hepatitis C virus or a hepatitis C virus like particle selected from:
• a hepatitis C virus derived from genotype 1a and said nucleic acid molecule encodes an amino acid sequence comprising one of the following groups of adaptive mutations:
• a) S2482G, N2651H, 12902L and H2986R according to SEQ ID NO:
• 25;
• or
• b) T2357A, S2375G, C2419R, M2834L and H2986R according to SEQ ID NO:
• 25;
• a hepatitis C virus derived from genotype 2a and said nucleic acid molecule encodes an amino acid sequence comprising the following adaptive mutations:
• K78E, V140L, T329S, H434N, A575T, A760T, V773A, V828A, A1146V, I1330V, L1500P, V1835I, T2000A, L2363P, A2367P, E2783Q and L3013S according to SEQ ID NO:
• 26;
• or
• a hepatitis C virus derived from genotype 3a and said nucleic acid molecule encodes an amino acid sequence comprising the following adaptive mutations:
• G395R, A856T, G875R, N1589S, 11753S, V2428A and D2807G according to SEQ ID NO:
• 27.