Variant analysis and immunogenicity prediction of envelope gene of HCV strains from China

Abstract

The putative envelope protein E2 of hepatitis C virus (HCV) is the most variable antigenic fragment in the whole viral genome and is responsible mainly for the large inter- and intra-individual heterogeneity of the infecting virus. To analyze variation and immunogenicity of HCV envelope genes of HCV strains from China, the serum samples from 12 Chinese patients with chronic hepatitis C from 10 cities of China were amplified, sequenced directly, and compared with international strains reported previously. Variant analysis and immunogenicity prediction were then carried out with computer programs. The results suggested that HCV envelope genes show diversity in the north and the south of China and that they vary among different genotypes. Therefore, the diversity among different genotypes and derived areas should be calculated for HCV vaccine design; simultaneously, domains characterized by the hydrophilicity and the conserved immunogenicity could be targeted, for example, the domain of aa434-444, aa408-414, aa449-462 in the envelope region and aa399-406 in HVR1. These data may hold the key for future development of HCV vaccine in China.

New trends of HCV infection in China revealed by genetic analysis of viral sequences determined from first-time volunteer blood donors

“…1). Although many reference sequences were included in the clusters, they were all of Chinese origin [14,17,[19][20][21][22]. Figure 1 provides an expanded view of cluster A and B (each is collapsed into a branch in the main tree) that were investigated previously and found to coincide with the ÔCultural RevolutionÕ in China [23].…”

Hepatitis C virus genotype distribution in China: Predominance of closely related subtype 1b isolates and existence of new genotype 6 variants

“…Phylogenetic tree based on E1 sequences of HCV subtype 1b isolates determined in this and other studies. Bold initials represent ten sequences reported by Cai et al [2002] (AH2: AF403231 isolated in Anhui province; SD2: AF403239 isolated in Shandong; SH2 and SH22: AF403234 and AF403237 isolated in Shanghai; ZJ2: AF403228 isolated in Zhejiang; HB2: AF403232 isolated in Hubei; BJ2: AF403236 isolated in Beijing; JX2: AF402571 isolated in Jiangxi; JS2: AF403239 isolated in Jiangsu; and SZ2: AF03238 isolated in Shenzhen). The eight accession numbers with geographic names in parenthesis indicate where these reference 1b sequences were isolated [Chen et al, 1992;Chou et al, 1993;Wang et al, 1993].…”

“…The eight accession numbers with geographic names in parenthesis indicate where these reference 1b sequences were isolated [Chen et al, 1992;Chou et al, 1993;Wang et al, 1993]. Isolate sh481 (this study) and AY194239 (Wuhan City) [Cai et al, 2002] of subtype 1a were used as outgroups. Percentages shown in italics represent bootstrap values and the bar at the base indicates the genetic distance per nucleotide site.…”

Broadly cross‐reactive mimotope of hypervariable region 1 of hepatitis C virus derived from DNA shuffling and screened by phage display library

“…In a previous study [Zhang et al, 2003], four DHFR-HVR1 fusion proteins were expressed successfully in prokaryotic cells, these HVR1 sequences were selected based on the immunogenicity predicted by computer analysis [Cai et al, 2002] and the most reactive sequence (aa 384-410 ATYTTGGAASHNTRGFTSLFSSGSQQK) showed positive with 66.7% (20/30) sera of HCV infected patients. To improve the cross reactivity, a method for the reassembly of sequences from their random DNA fragments by DNA shuffling, resulting in vitro recombination is reported in this paper.…”