Molecular characterization of hepatitis C virus genotype 2a from the entire sequences of four isolates

Genotype 2a hepatitis C virus (HCV) has different characteristics from geno type 1b, such as responsiveness to interferon therapy. Such type-specific c haracteristics appear to be due to differences in the HCV genome sequence. The complete sequences of genotype 2a HCV genome isolated from four patient s with chronic hepatitis C were determined, and nucleotide and deduced amin o acid sequences were compared within genotype 2a, as well as between genot ype 20 and 1b. Whereas the amino acid sequence similarity of the core regio n was highest within genotype 1b, the NS3 and NS4B regions of exhibited gre ater similarity than the core region in genotype 2a. The serine protease an d helicase motifs in the NS3 region were well conserved in genotype 2a to t he same degree as in genotype 1b. However, the putative secondary structure of 2a isolates was significantly different from that of the 1b isolates. A nalysis of amino acid similarity between genotypes 2a and 1b revealed the l owest degree of similarity in the E1 region, followed by the NS2 and NS5A r egion. Sequences of genotype 2a in the interferon-sensitivity determining r egion (ISDR) located in the NS5A region had a deletion of four amino acids compared with that of genotype 1b. When the ISDR of the genotype 2a was ali gned for maximal similarity, it exhibited similarity of only 52.5-55.0% whe n compared with that of HCV-J, which belongs to genotype 1b. These findings for the entire sequences of genotype 2a isolates will contribute to virolo gical studies of HCV. J. Med. Virol. 64:466-475, 2001. 2001 Wiley-Liss, Inc .