Hepatitis C virus variants from Nepal with novel genotypes and their classification into the third major group

Five isolates of hepatitis C virus (HCV) RNA from patients with chronic liver disease in Nepal were not classifiable into the known genotypes I/1a, II/1b, III/2a, IV/2b or V/3a using PCR with type-specific primers deduced from the HCV core gene. Their nucleotide sequences were determined for the 5'-terminal 1.5 kilobases and 3'-terminal 1.2 kilobases, covering 30% of the entire genome, and compared with each other and with reported sequences of HCV isolates of various genotypes. They were more similar to a reported HCV isolate (NZL1) of genotype V/3a (in 81.6 to 84.1% of their nucleotides and 85.7 to 88.7% of the deduced amino acid sequence) compared with the genotypes I/1a to IV/2b (in 69.3 to 74.7% and 72.3 to 77.4%, respectively). Hence they were considered to be variants of the third major group (group 3). The five HCV isolates shared 81.3 to 85.2% of nucleotide sequence and 85.4 to 89.3% of deduced amino acid sequence. Thus they were substantially different from each other. One of them was classified as genotype VI/3b due to an 88.2% similarity in nucleotide sequence to that of the reported HCV isolates of this genotype, whereas the remaining four were classified into provisional genotypes 3c, 3d, 3e and 3f. These HCV variants have evolved and remained in Nepal, and have not been observed in the other areas of the world.