目的 利用生物信息学方法对H5N8高致病性禽流感病毒血凝素(hemagglutinin,HA)蛋白的T细胞的优势抗原表位进行预测,探索高致病性禽流感抗原表位快速预测方法.方法 以甲型流感病毒[A/chicken/Moscow/94/2017(H5N8),ID:ATE48581.1]为原始毒株,从GenBank数据库中获取其血凝素(hemagglutinin,HA)蛋白的氨基酸序列,综合应用多个生物信息学工具对HA蛋白潜在的细胞毒性T细胞(cytotoxic T lymphocyte,CTL)表位和辅助 T细胞(helper T lymphocyte,HTL)表位进行预测.结果 H5N8高致病性禽流感病毒的HA蛋白保守性较高,44条不同病毒株HA蛋白可以装进同一系统进化枝.经预测,HA蛋白的一级、二级结构明确,三级结构模型可信度高,构象合理.最终筛选到具有免疫原性且抗原性较好、无致敏性、无毒性的CTL表位8条,筛选到抗原性较好、无致敏性、无毒性、能诱导γ-干扰素(interferon-y,IFN-γ)、白介素4(interleukin 4,IL-4)分泌的HTL表位8条.预测的16条表位在不同的44条H5N8蛋白序列之间的保守性最好,在10条H5N6的HA蛋白序列之间的保守性次之,在13条H5N1的HA蛋白序列之间保守性较差.结论 通过本研究的预测流程可以快速筛选出HA蛋白的CTL表位和HTL抗原表位,为快速高效研发新型重组多肽流感疫苗提供了技术路线和理论参考.
Abstract
Objective To explore the rapid prediction method of highly pathogenic avian influenza(HPAI)anti-gen epitope through predicting the dominant T cell epitopes of hemagglutinin(HA)proteins of H5N8 highly pathogenic influenza virus.Methods The amino acid sequence of HA protein from the HPAI H5N8 virus strain A/chicken/Moscow/94/2017(GenBank ID:ATE48581.1)was obtained from the GenBank database.Mul-tiple bioinformatics tools were used to predict the potential cytotoxic T lymphocyte(CTL)and helper T lympho-cyte(HTL)epitopes of HA protein.Results The HA protein of the HPAI H5N8 virus exhibited high conserva-tion,with 44 HA proteins from different virus strains that could be assembled into the same phylogenetic clade.The primary and secondary structures of HA protein were clear,and the tertiary structure model had high reliabil-ity and reasonable conformation.Eight CTL epitopes with good immunogenicity,antigenicity,non-allergenicity and non-toxicity and 8 HTL epitopes with good antigenicity,non-allergenicity and non-toxicity,which could in-duce interferon-γ(IFN-γ)and interleukin 4(IL-4)secretion were identified.The 16 predicted epitopes were best conserved among 44 different H5N8 HA protein sequences,followed by 10 H5N6 HA protein sequences,and had relatively poor conservation among the 13 H5N1 HA protein sequences.Conclusion The CTL and HTL epitope of HA protein can be quickly screened out through the prediction process,which provides a techni-cal route and theoretical reference for the rapid and efficient development of a new recombinant polypeptide influ-enza vaccine.
维普
万方数据