Bioinformatics Division, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
Virol J. 2011 Feb 8;8:55. doi: 10.1186/1743-422X-8-55.
HCV is a positive sense RNA virus affecting approximately 180 million people world wide and about 10 million Pakistani populations. HCV genotype 3a is the major cause of infection in Pakistani population. One of the major problems of HCV infection especially in the developing countries that limits the limits the antiviral therapy is the long term treatment, high dosage and side effects. Studies of antigenic epitopes of viral sequences of a specific origin can provide an effective way to overcome the mutation rate and to determine the promiscuous binders to be used for epitope based subunit vaccine design. An in silico approach was applied for the analysis of entire HCV proteome of Pakistani origin, aimed to identify the viral epitopes and their conservancy in HCV genotypes 1, 2 and 3 of diverse origin.
Immunoinformatic tools were applied for the predictive analysis of HCV 3a antigenic epitopes of Pakistani origin. All the predicted epitopes were then subjected for their conservancy analysis in HCV genotypes 1, 2 and 3 of diverse origin (worldwide). Using freely available web servers, 150 MHC II epitopes were predicted as promiscuous binders against 51 subjected alleles. E2 protein represented the 20% of all the predicted MHC II epitopes. 75.33% of the predicted MHC II epitopes were (77-100%) conserve in genotype 3; 47.33% and 40.66% in genotype 1 and 2 respectively. 69 MHC I epitopes were predicted as promiscuous binders against 47 subjected alleles. NS4b represented 26% of all the MHC I predicted epitopes. Significantly higher epitope conservancy was represented by genotype 3 i.e. 78.26% and 21.05% for genotype 1 and 2.
The study revealed comprehensive catalogue of potential HCV derived CTL epitopes from viral proteome of Pakistan origin. A considerable number of predicted epitopes were found to be conserved in different HCV genotype. However, the number of conserved epitopes in HCV genotype 3 was significantly higher in contrast to its conservancy in HCV genotype 1 and 2. Despite of the lower conservancy in genotype 1 and 2, all the predicted epitopes have important implications in diagnostics as well as CTL-based rational vaccine design, effective for most population of the world and especially the Pakistani population.
HCV 是一种正链 RNA 病毒，影响着全球约 1.8 亿人和 1000 万巴基斯坦人。HCV 基因型 3a 是巴基斯坦人群感染的主要原因。HCV 感染的一个主要问题，特别是在发展中国家，限制了抗病毒治疗的是长期治疗、高剂量和副作用。对特定来源的病毒序列抗原表位的研究可以提供一种有效的方法来克服突变率，并确定用于基于表位的亚单位疫苗设计的混杂结合物。应用生物信息学方法对巴基斯坦起源的 HCV 全长蛋白进行了分析，旨在鉴定 HCV 基因型 1、2 和 3 中不同起源的病毒表位及其保守性。
应用免疫信息学工具对巴基斯坦起源的 HCV 3a 抗原表位进行了预测分析。然后对所有预测的表位在来自不同地区（全球）的 HCV 基因型 1、2 和 3 中进行了保守性分析。使用免费的网络服务器，预测了 150 个 MHC II 表位作为针对 51 个被测试等位基因的混杂结合物。E2 蛋白代表了所有预测的 MHC II 表位的 20%。在基因型 3 中，75.33%的预测 MHC II 表位（77-100%）是保守的；在基因型 1 和 2 中，分别有 47.33%和 40.66%是保守的。预测了 69 个 MHC I 表位作为针对 47 个被测试等位基因的混杂结合物。NS4b 代表了所有预测的 MHC I 表位的 26%。基因型 3 的表位保守性显著较高，即基因型 1 和 2 的分别为 78.26%和 21.05%。
该研究揭示了来自巴基斯坦起源的 HCV 病毒蛋白的全面潜在 CTL 表位目录。在不同的 HCV 基因型中发现了相当数量的保守表位。然而，与 HCV 基因型 1 和 2 相比，HCV 基因型 3 中的保守表位数量显著更高。尽管在基因型 1 和 2 中的保守性较低，但所有预测的表位在诊断以及基于 CTL 的合理疫苗设计方面都具有重要意义，对世界上大多数人群，特别是对巴基斯坦人群有效。
