Full-genome Nucleotide Sequence of a Hepatitis C Virus Variant (Isolate Name VAT96) Representing a New Subtype within the Genotype 2 (Arbitrarily 2k)

Hepatitis C virus (HCV), a single-stranded RNA virus of the family Flaviviridae, has a wide range of genetic heterogeneity: 6–11 genotypes (or 6 clades) have been known and each genotype comprises multiple subtypes. Here we report the entire nucleotide sequence of an HCV isolate from a patient in Moldova with chronic hepatitis (isolate name VAT96). The genetic organization of VAT96 was, from 5′ to 3′ ends, 5′UTR (341 nt), polyprotein ORF (9099 nt), 3′UTR (38 nt except for the poly-U and poly-pyrimidine stretch), and X-tail (98 nt). Comparison of the polyprotein amino acid sequence of VAT96 with those of known full-genome isolates assigned VAT96 to the genotype 2 (or clade 2), and further phylogenetic analysis based on a 447-nt sequence that covers part of the C and E1 regions suggested that VAT96 represents a new subtype within the genotype 2, arbitrarily designated “2k” VAT96 was unique in that it possessed a U residue prior to GCC at the 5′ end of its genome while all the other full-genome HCV sequences start with GCC or ACC. In addition, the polyprotein ORF of HCV-VAT96, like HCV-BEBE1 of 2c, encoded several additional amino acids in excess, compared to 2a and 2b sequences. Despite these characteristics that may be unique to VAT96, the 98-nt sequence of the X-tail of VAT96 was highly homologous to those of other isolates with different genotypes so far reported.

[1]  P. Laurent-Puig,et al.  Hepatitis C virus genotyping by means of 5'-UR/core line probe assays and molecular analysis of untypeable samples. , 1995, Virus research.

[2]  S. Mishiro,et al.  Full-length genomic sequence of a hepatitis C virus genotype 2c isolate (BEBE1) and the 2c-specific PCR primers , 2005, Archives of Virology.

[3]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[4]  T. Gojobori,et al.  Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization , 1998, Archives of Virology.

[5]  E. Holmes,et al.  Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. , 1993, The Journal of general virology.

[6]  N. Kato,et al.  Genetic analysis of the hepatitis C virus (HCV) genome from HCV-infected human T cells. , 1997, The Journal of general virology.

[7]  N. Kato,et al.  Structure of the 3' terminus of the hepatitis C virus genome , 1996, Journal of virology.

[8]  H. Okamoto,et al.  Nucleotide sequence of the genomic RNA of hepatitis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions. , 1991, The Journal of general virology.

[9]  S. Mishiro,et al.  Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. , 1992, Virology.

[10]  T. Tsuji,et al.  Genetic organization and diversity of the 3' noncoding region of the hepatitis C virus genome. , 1996, Virology.

[11]  P. Simmonds,et al.  Complete coding sequence of hepatitis C virus genotype 6a. , 1997, Biochemical and biophysical research communications.

[12]  C. Rice,et al.  Identification of a highly conserved sequence element at the 3' terminus of hepatitis C virus genome RNA , 1996, Journal of virology.

[13]  S. Mishiro,et al.  Genetic heterogeneity of hepatitis C virus. , 1994, Intervirology.

[14]  M. Sakamoto,et al.  Entire nucleotide sequence and characterization of a hepatitis C virus of genotype V/3a. , 1994, The Journal of general virology.

[15]  M. Sakamoto,et al.  The entire nucleotide sequence and classification of a hepatitis C virus isolate of a novel genotype from an Indonesian patient with chronic liver disease. , 1994, The Journal of general virology.

[16]  P. Simmonds,et al.  The complete coding sequence of hepatitis C virus genotype 5a, the predominant genotype in South Africa. , 1997, Biochemical and biophysical research communications.

[17]  P. Simmonds,et al.  Complete nucleotide sequence of a type 4 hepatitis C virus variant, the predominant genotype in the Middle East. , 1997, The Journal of general virology.

[18]  F Tsuda,et al.  The entire nucleotide sequences of three hepatitis C virus isolates in genetic groups 7-9 and comparison with those in the other eight genetic groups. , 1998, The Journal of general virology.

[19]  Y. Ito,et al.  Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability. , 1992, Virology.

[20]  Matthew J. Brauer,et al.  Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. , 1991, Virology.

[21]  H. Okamoto,et al.  Hepatitis C virus variants from Jakarta, Indonesia classifiable into novel genotypes in the second (2e and 2f), tenth (10a) and eleventh (11a) genetic groups. , 1996, The Journal of general virology.

[22]  N. V. Doroshenko,et al.  Prevalence of hepatitis C virus and distribution of its genotypes in Northern Eurasia , 2005, Archives of Virology.

[23]  K. Chayama,et al.  Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C. , 1994, The Journal of general virology.

[24]  N Enomoto,et al.  Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. , 1996, The New England journal of medicine.

[25]  W. Quint,et al.  Sequence analysis of hepatitis C virus genotypes 1 to 5 reveals multiple novel subtypes in the Benelux countries. , 1995, The Journal of general virology.