Polynucleotide derived from novel hepatitis c virus strain and use thereof

Abstract

A polynucleotide encoding the amino acid shown in SEQ ID NO:2 or SEQ ID NO: 5, or encoding an amino acid sequence having not less than 98% identity thereto; preferably a polynucleotide comprising replacement of the amino acid corresponding to glutamic acid at position 1202 of SEQ ID NO:2 (position 177 of SEQ ID NO:5) with glycine, replacement of the amino acid corresponding to glutamic acid at position 1056 (position 31 of SEQ ID NO:5) with valine, and replacement of the amino acid corresponding to alanine at position 2199 (position 1174 of SEQ ID NO:5) with threonine.

What is claimed is: 
     
         1 . A method of screening or evaluating a drug candidate substance which inhibits replication or protein translation of HCV, comprising
 administering or adding said drug candidate substance to a non-human mammal or an isolated cell to which a recombinant polynucleotide has been introduced and which produces a recombinant HCV and   evaluating replication capacity of HCV or capacity of translation of HCV protein, wherein said recombinant polynucleotide encodes an amino acid sequence having at least 99% identity to the entire sequence set forth in SEQ ID NO:2 and said amino acid sequence comprises a glutamic acid to glycine substitution at position 1202 of SEQ ID NO:2.   
     
     
         2 . The method according to  claim 1 , wherein the amino acid sequence encoded by the recombinant polynucleotide further comprises a serine to proline substitution at position 2321 and a leucine to phenylalanine substitution at position 2889 of SEQ ID NO:2. 
     
     
         3 . The method according to  claim 1 , wherein said polynucleotide comprises a nucleotide sequence at least 95% identical to the entire sequence set forth in SEQ ID NO:1 and wherein, in cases where the polynucleotide is RNA, the nucleotide “t” in said sequence is replaced with a “u”. 
     
     
         4 . The method according to  claim 2 , wherein said polynucleotide comprises a nucleotide sequence at least 95% identical to the entire sequence set forth in SEQ ID NO:1 and wherein, in cases where the polynucleotide is RNA, the nucleotide “t” in said sequence is replaced with a “u”. 
     
     
         5 . The method according to  claim 1 , wherein said non-human mammal is a human hepatocyte chimeric mouse. 
     
     
         6 . A method of screening or evaluating a drug candidate substance which inhibits replication or protein translation of HCV, comprising
 administering or adding said drug candidate substance to a non-human mammal or an isolated cell to which a recombinant polynucleotide has been introduced and which produces a recombinant HCV and   evaluating replication capacity of HCV or capacity of translation of HCV protein, wherein said recombinant polynucleotide encodes an amino acid sequence having at least 98% identity to the entire sequence set forth in SEQ ID NO:2 and said amino acid sequence comprises a glutamic acid to glycine substitution at position 1202, a glutamic acid to valine substitution at position 1056, and a alanine to threonine substitution at position 2199 of SEQ ID NO:2.   
     
     
         7 . The method according to  claim 6 , wherein the amino acid sequence encoded by the recombinant polynucleotide further comprises a serine to proline substitution at position 2321 and a leucine to phenylalanine substitution at position 2889 of SEQ ID NO:2. 
     
     
         8 . The method according to  claim 6 , wherein said polynucleotide comprises a nucleotide sequence at least 95% identical to the entire sequence set forth in SEQ ID NO:1 and wherein, in cases where the polynucleotide is RNA, the nucleotide “t” in said sequence is replaced with a “u”. 
     
     
         9 . The method according to  claim 7 , wherein said polynucleotide comprises a nucleotide sequence at least 95% identical to the entire sequence set forth in SEQ ID NO:1 and wherein, in cases where the polynucleotide is RNA, the nucleotide “t” in said sequence is replaced with a “u”. 
     
     
         10 . The method according to  claim 6 , wherein said non-human mammal is a human hepatocyte chimeric mouse.