人肠道病毒71型和柯萨奇病毒A16型B细胞线性表位的生物信息学预测
PDF下载 (346)高柳莺,祝 苗,戎 浩,董长征.人肠道病毒71型和柯萨奇病毒A16型B细胞线性表位的生物信息学预测[J].宁波大学学报(理工版),2019,32(2):54-60.DOI:
GAO Liu-ying,ZHU Miao,RONG Hao,DONG Chang-zheng.A bioinformatics method for prediction of B cellular linear epitopes for human enterovirus 71 and Coxsackievirus A16[J].Journal of Ningbo University(Natural Science & Engineering Edition),2019,32(2):54-60.DOI:
| Title: | A bioinformatics method for prediction of B cellular linear epitopes for human enterovirus 71 and Coxsackievirus A16 |
| 作者: | 高柳莺, 祝 苗, 戎 浩, 董长征 |
| Author(s): | GAO Liu-ying, ZHU Miao, RONG Hao, DONG Chang-zheng |
| 关键词: | 肠道病毒71型; 柯萨奇病毒A16型; B细胞线性表位; 抗原表位; 生物信息学; 手足口病 |
| Keywords: | enterovirus 71 (EV71); Coxsackievirus A16 (CVA16); B cellular linear epitopes; antigenic epitopes; bioinformatics; hand, foot and mouth disease |
| 分类号: | R183 |
| 文献标识码: | A |
| 摘要: | 发展了人肠道病毒B细胞线性表位(简称线性表位)的生物信息学预测算法, 系统性地预测和比较了人肠道病毒71型(Enterovirus 71, EV71)和柯萨奇病毒A16型(Coxsackievirus A16, CVA16)的线性表位. 结果显示: EV71和CVA16结构蛋白(Viral Protein, VP)上都有16个线性表位, 2种肠道病毒的线性表位的位置高度一致, 但氨基酸序列保守性较低, 大多数表位都存在至少3个氨基酸残基的差异, 提示2种病毒的线性表位具有血清型特异性, 这很可能是两者不能交叉反应的原因. 线性表位主要分布在β链之间的环上和C-末端, 分别有13个(81.3％)和2个(12.5％)表位. 与文献报道相比较, 16个线性表位中, 分别有6个(37.5％)EV71和12个(75％)CVA16的表位已被实验验证. 特别是实验研究重点关注的VP1, 6个预测表位中, 分别有4个(66.7％)EV71的预测表位和5个(83.3％)CVA16的预测表位已被实验所验证. 说明算法具有较高的预测可靠度. 线性表位的实验研究主要集中在VP1, 预测结果提示VP2和VP3也能形成表位, 应该加以重视. 生物信息学算法通过预测和筛选潜在的线性表位, 能够大大降低实验负荷, 为包括EV71和CVA16在内的人肠道病毒的研究提供有力支持. 对肠道病毒线性表位的预测, 有助于更好地监测和预警手足口病疫情, 辅助疫苗的研发和准备. |
| Abstract: | A bioinformatics method was developed to predict the B cellular linear epitopes for human enteroviruses. The linear epitopes of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) were systematically predicted and compared. The results show that both EV71 and CVA16 had 16 linear epitopes in structural proteins (VPs). Although the positions of the epitopes were highly accordant, the homologies of the amino acid sequences were less conservative and there were at least three mutations for the majority of the epitopes. This implied that the epitopes were serotype-specific and caused the low titers of cross-reactivity. The loops between the β strands (13/16, 81.3%) and the C-terminals (2/16, 12.5%) were discovered as being enrichment of the epitopes. Among 16 epitopes, 6 (37.5%) of EV71 epitopes and 12 (75%) of CVA16 epitopes had been verified by the previously reported experiments. According to 6 predicted epitopes in VP1, 4 of EV71 (66.7%) and 5 of CVA16 (83.3%) had been verified respectively. The evidences showed that the bioinformatics prediction method was reliable. Since most of previous studies focused on the epitopes of VP1, the current studies suggested that more studies should focus on VP2 and VP3. The bioinformatics method could predict and filter the potential epitopes that would reduce the strength of the experiments. It may help the studies on human enteroviruses including EV71 and CVA16. Furthermore, the prediction of the linear epitopes of the enteroviruses could also support the surveillance and the early warning of the breaks of the hand, foot and mouth disease as well as the R&D and preparation of vaccines. |
| 参考文献 /References: | [1] 刘志芳, 桂娟娟, 华启航, 等. 人肠道病毒71型与手足口病的分子流行病学及其分子进化[J]. 遗传, 2015, 37(5):426-435. [2] Li R, Liu L, Mo Z, et al. An inactivated enterovirus 71 vaccine in healthy children[J]. New England Journal of Medicine, 2014, 370(9):829-837. [3] Zhu F, Xu W, Xia J, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China[J]. New England Journal of Medicine, 2014, 370(9):818- 828. [4] 祝苗, 张添方, 高柳莺, 等. 人肠道病毒71型抗原表位的研究进展[J]. 中国细胞生物学学报, 2017, 39(9): 1243-1250. [5] Huang Y, Liao J, Yen L, et al. Japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges[EB/OL]. [2018-05-10]. https://jbiomedsci.biomedcentral.com/articles/ 10.1186/s12929-015-0181-8. [6] Xue C, Tian X, Li X, et al. Construction and characterization of a recombinant human adenovirus type 3 vector containing two foreign neutralizing epitopes in hexon[J]. Virus Research, 2014, 183(7):67-74. [7] Foo D G, Alonso S, Phoon M C, et al. Identification of neutralizing linear epitopes from the VP1 capsid protein of enterovirus 71 using synthetic peptides[J]. Virus Research, 2007, 125(1):61-68. [8] Lim X, Jia Q, Khong W, et al. Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection[EB/OL]. [2018-05-10]. https:// journals.plos.org/plosone/article?id=10.1371/journal.pon 0029751. [9] Parker J M, Guo D, Hodges R S. New hydrophilicity scale derived from high-performance liquid chromate- graphy peptide retention data: Correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites[J]. Biochemistry, 1986, 25(19):5425-5432. [10] Emini E A, Hughes J V, Perlow D S, et al. Induction of hepatitis a virus-neutralizing antibody by a virus-specific synthetic peptide[J]. Journal of Virology, 1985, 55(3): 836-839. [11] Karplus P A, Schulz G E. Prediction of chain flexibility in proteins[J]. Naturwissenschaften, 1985, 72(4):212-213. [12] Chou P Y, Fasman G D. Prediction of the secondary structure of proteins from their amino acid sequence[J]. Advances in Enzymology & Related Areas of Molecular Biology, 1978, 47(6):45-148. [13] Kolaskar A S, Tongaonkar P C. A semi-empirical method for prediction of antigenic determinants on protein antigens[J]. FEBS Letters, 1990, 276(1):172-174. [14] Larsen J E, Lund O, Nielsen M. Improved method for predicting linear B-cell epitopes[EB/OL]. [2018-05-10]. https://immunome-research.biomedcentral.com/articles/ 10.1186/1745-7580-2-2. [15] Xiao C, Rossmann M G. Interpretation of electron density with stereographic roadmap projections[J]. Journal of Structural Biology, 2007, 158(2):182-187. [16] Larkin M A, Blackshields G, Brown N P, et al. Clustal W and clustal X version 2.0[J]. Bioinformatics, 2007, 23(21): 2947-2948. [17] Foo D G, Ang R X, Alonso S, et al. Identification of immunodominant VP1 linear epitope of enterovirus 71 (EV71) using synthetic peptides for detecting human anti-EV71 IgG antibodies in western blots[J]. Clinical Microbiology & Infection, 2008, 14(3):286-288. [18] Zhang J, Dong M, Jiang B, et al. Antigenic characteristics of the complete and truncated capsid protein VP1 of enterovirus 71[J]. Virus Research, 2012, 167(2):337-342. [19] Liu C, Chou A, Lien S, et al. Identification and characterization of a cross-neutralization epitope of enterovirus 71[J]. Vaccine, 2011, 29(26):4362-4372. [20] Ku Z, Ye X, Shi J, et al. Single neutralizing monoclonal antibodies targeting the VP1 GH loop of enterovirus 71 inhibit both virus attachment and internalization during viral entry[J]. Journal of Virology, 2015, 89(23):12084- 12095. [21] Chang G, Luo Y, Wu X, et al. Monoclonal antibody induced with inactived EV71-Hn2 virus protects mice against lethal EV71-Hn2 virus infection[EB/OL]. [2018- 05-10]. https://virologyj.biomedcentral.com/articles/10.1186/ 1743-422X-7-106. [22] Xu L, He D, Li Z, et al. Protection against lethal enterovirus 71 challenge in mice by a recombinant vaccine candidate containing a broadly cross-neutralizing epitope within the VP2 EF loop[J]. Theranostics, 2014, 4(5):498-513. [23] Shi J, Huang X, Liu Q, et al. Identification of conserved neutralizing linear epitopes within the VP1 protein of coxsackievirus A16[J]. Vaccine, 2013, 31(17):2130-2136. [24] 高孟, 倪红霞, 朱莲, 等. 柯萨奇病毒A16型衣壳蛋白VP1-VP3的B淋巴细胞线性抗原表位预测与确定[J]. 中华临床感染病杂志, 2015, 8(6):543-548. [25] Kiener T K, Jia Q, Lim X, et al. Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein[EB/OL]. [2018-05-10]. https://virologyj.Biomed central.com/articles/10.1186/1743-422X-9-55. [26] Xu L, He D, Yang L, et al. A broadly cross-protective vaccine presenting the neighboring epitopes within the VP1 GH loop and VP2 EF loop of enterovirus 71[EB/OL]. [2018-05-10]. https://www.nature.com/articles/srep12973. [27] Gong M, Zhu H, Zhou J, et al. Cryo-electron microscopy study of insect cell-expressed enterovirus 71 and coxsackievirus A16 virus-like particles provides a structural basis for vaccine development[J]. Journal of Virology, 2014, 88(11):6444-6452. [28] Lyu K, He Y, Li H, et al. Crystal structures of yeast-produced enterovirus 71 and enterovirus 71/ coxsackievirus A16 chimeric virus-like particles provide the structural basis for novel vaccine design against hand-foot-and-mouth disease[J]. Journal of Virology, 2015, 89(12):6196-6208. [29] 蒋建平, 王来, 李宜川, 等. 肠道病毒71型VP1外壳蛋白二级结构及B细胞表位预测[J]. 山东医药, 2009, 49(35):10-12. [30] 俞海洋, 陈伟, 倪德群, 等. 肠道病毒71型六安地区分离株VP1基因的生物信息学分析及B细胞表位预测[J]. 安徽医科大学学报, 2012, 47(3):233-240. [31] Chen Y, Li C, He D, et al. Antigenic analysis of divergent genotypes human enterovirus 71 viruses by a panel of neutralizing monoclonal antibodies: Current genotyping of EV71 does not reflect their antigenicity[J]. Vaccine, 2013, 31(2):425-430. [32] Ye X, Ku Z, Liu Q, et al. Chimeric virus-like particle vaccines displaying conserved enterovirus 71 epitopes elicit protective neutralizing antibodies in mice through divergent mechanisms[J]. Journal of Virology, 2014, 88(1):72-81. |
| 备注/Memo: | 收稿日期: 2018－07－24. 宁波大学学报（理工版）网址: http://journallg.nbu.edu.cn/ 基金项目: 浙江省基础公益研究计划项目（LGF18C060001）; 浙江省教育厅科研项目（Y201533182）; 宁波市自然科学基金（2018A610240）; 宁波大学研究生科研创新基金; 宁波大学大学生科研创新计划（2018SRIP1913; 2018SRIP1916）. 第一作者: 高柳莺（1992－）, 女, 浙江嘉兴人, 在读硕士研究生, 主要研究方向: 生物信息学. E-mail: 854709337@qq.com *通信作者: 董长征（1978－）, 男, 浙江丽水人, 博士/副教授, 主要研究方向: 生物信息学. E-mail: dongchangzheng@nbu.edu.cn 宁波大学学报（理工版）网址：http://journallg.nbu.edu.cn/ |
