GENETIC-VARIABILITY AND CHARACTERIZATION OF NONSTRUCTURAL REGION-5 OFHEPATITIS-C VIRUS GENOME FROM CHINESE PATIENTS

Sequence variation in the putative nonstructural region 5b (NS5b) of h epatitis C virus (HCV) was analyzed in China. Complementary DNA fragme nts from sera of 49 Chinese patients were amplified by polymerase chai n reaction (PCR) and the products were cloned and sequenced. Based on the comparison in NS5b of 33 clones of genotype 1b and 16 clones of ge notype 2a, Chinese isolates of HCV belong to the same subtype as HCV-J , and HC-J6 from Japan. There does exist, however, some heterogeneity in the primary structure of the nucleotide acid. Higher homology was f ound among Chinese isolates than among Chinese isolates and Japanese i solates. Furthermore. among Chinese isolates, we found some conserved nucleotide acid positions different from those of Japanese isolates. C omparison of average homology among the 33 clones of genotype 1b and t he 16 clones of genotype 2a indicated that the average homology among genotype 2a was lower than that among genotype 1b. In addition, a dele tion of three nucleotide acids and a frame-shift, resulting in the int roduction of an in-frame stop codon, were first observed in the NS5b r egion. These results indicated geographical differences in the distrib ution of individual HCV isolates, and the existence of a local variant in the same subtype. Our findings also suggested the need for further study on the sequence of genotype 2a, to improve diagnosis and help t o advance the development of a vaccine.