Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Graduate School of Biomedical and Health Science, 1-2-3, Kasumi, Minami-ku, Hiroshima-shi 734-8551, Japan.
Department of Health, Binh Thuan Medical College, Binh Thuan Province, 274 Nguyen Hoi Street, Phan Thiet City 800000, Vietnam.
Viruses. 2020 May 16;12(5):551. doi: 10.3390/v12050551.
The high genetic variability of hepatitis C virus (HCV) is the main obstacle to developing a vaccine. E2 has attracted attention for vaccine development because targeting this protein could potentially overcome issues related to the genetic diversity of HCV. In this study, we analyzed HCV genes in the general population of Cambodia and investigated the E2 locus as a candidate for vaccine development. HCV sero-epidemiological surveys were conducted between the period 2010 and 2014, with an HCV RNA-positive rate of 1.3% (11/868). Follow-up blood samples were collected from four anti-HCV- and HCV RNA- positive patients (genotype 1b: 2 cases, 6e: 1 case, 6r: 1 case) after 4.12 years. Analysis of HCV full-length nucleotide sequences in paired specimens revealed that the mutation rates of HCV genotypes 1b and 6e/6r were 1.61-2.03 × 10 and 2.52-2.74 × 10 substitutions/site/year, respectively. Non-synonymous substitutions were detected in HVR1, the front layer of the CD81 binding site, and the β-sandwich, but not in the N-terminal region or adjacent to the CD81 binding site. Therefore, we conclude that the CD81 binding site is a promising locus for HCV vaccine development.
丙型肝炎病毒 (HCV) 的高遗传变异性是开发疫苗的主要障碍。E2 因其作为疫苗开发的靶向目标而受到关注，因为针对该蛋白可能有助于克服 HCV 遗传多样性相关的问题。在这项研究中，我们分析了柬埔寨普通人群中的 HCV 基因，并研究了 E2 基因座作为疫苗开发的候选者。2010 年至 2014 年期间进行了 HCV 血清流行病学调查，HCV RNA 阳性率为 1.3%（868 例中的 11 例）。从 4 例抗 HCV 和 HCV RNA 阳性患者（基因型 1b：2 例，6e：1 例，6r：1 例）中采集了 4.12 年后的随访血样。对配对标本中的 HCV 全长核苷酸序列进行分析发现，基因型 1b 和 6e/6r 的 HCV 突变率分别为 1.61-2.03×10 和 2.52-2.74×10 个替换/位点/年。在 HVR1、CD81 结合位点的前层和 β-夹层中检测到非同义替换，但在 N 端区域或 CD81 结合位点附近未检测到。因此，我们得出结论，CD81 结合位点是开发 HCV 疫苗的有前途的候选者。
