Differences in hepatitis C virus core protein processing among genotypes 1 and 2

Two forms of hepatitis C virus (HCV) core protein, p23 and p21, are produced from a precursor polyprotein. Production of p21 by cleavage at the c-terminus of p23 is considered essential for viral assembly and replication. In the present experiment, an in vitro translation and transcription assays were used to examine cleavage of p21 from p23 among 19 clones isolated from patients with chronic hepatitis, including 10 infected with genotype 1, and nine infected with genotype 2. Significantly greater p21 to p23 ratios were observed among genotype 1 clones, compared to genotype 2 clones. A comparison of the amino acid sequences of these clones revealed greater production of p21 core protein among clones which contained alanine, rather than valine, at amino acid residue 189. An exploration of Hepatitis Virus Database revealed that efficient p21 production related alanine at amino acid position 189 was observed in most clones of genotype 1 and in rare clones of genotype 2. These data suggest that the efficiency of core protein production differs among genotypes depending on differences in the c-terminus amino acid sequences of their core region. This may explain differences in some of the clinical characteristics of various genotypes or clones. (C) 2004 Elsevier B.V. All rights reserved.