H5N8高致病性禽流感病毒HA蛋白T细胞抗原表位的预测  

Prediction of T cell epitope antigen for hemagglutinin protein of highly pathogenic H5N8 avian influenza virus

作　　者：杨亚龙 杨森 姚树森[4] 徐风华[1] YANG Yalong;YANG Sen;YAO Shusen;XU Fenghua(Pharmaceutical Sciences Research Division,Department of Pharmacy,Medical Supplies Center,PLA General Hospital,PLA Medical School,Beijing 100853,China;不详)

机构地区：[1]解放军总医院药剂科药学基础研究室,北京100853 [2]解放军医学院,北京100853 [3]武警北京市总队医院,北京100027 [4]解放军总医院医疗保障中心,北京100853

出　　处：《中国病毒病杂志》2024年第3期260-266,共7页Chinese Journal of Viral Diseases

基　　金：国家自然科学基金面上项目(82171814)。

摘　　要：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-γ,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。Objective To explore the rapid prediction method of highly pathogenic avian influenza(HPAI)antigen 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.Multiple bioinformatics tools were used to predict the potential cytotoxic T lymphocyte(CTL)and helper T lymphocyte(HTL)epitopes of HA protein.Results The HA protein of the HPAI H5N8 virus exhibited high conservation,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 reliability 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 induce 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 technical route and theoretical reference for the rapid and efficient development of a new recombinant polypeptide influenza vaccine.

关 键 词：生物信息学 多肽疫苗 CTL候选表位 HTL候选表位 H5N8 血凝素 

分 类 号：R392[医药卫生—免疫学]