Computational approach for predicting the conserved B-cell epitopes of hemagglutinin H7 subtype influenza virus

Wang,Xiangyu; Sun,Qi; Ye,Zhonghua; Hua,Ying; Shao,Na; Du,Yanli; Zhang,Qiwei; Wan,Chengsong

doi:10.3892/etm.2016.3636

Computational approach for predicting the conserved B-cell epitopes of hemagglutinin H7 subtype influenza virus

Authors:
- Xiangyu Wang
- Qi Sun
- Zhonghua Ye
- Ying Hua
- Na Shao
- Yanli Du
- Qiwei Zhang
- Chengsong Wan
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Affiliations: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: August 31, 2016 https://doi.org/10.3892/etm.2016.3636
Pages: 2439-2446
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An avian-origin influenza H7N9 virus epidemic occurred in China in 2013‑2014, in which >422 infected people suffered from pneumonia, respiratory distress syndrome and septic shock. H7N9 viruses belong to the H7 subtype of avian‑origin influenza viruses (AIV-H7). Hemagglutinin (HA) is a vital membrane protein of AIV that has an important role in host recognition and infection. The epitopes of HA are significant determinants of the regularity of epidemic and viral mutation and recombination mechanisms. The present study aimed to predict the conserved B‑cell epitopes of AIV‑H7 HA using a bioinformatics approach, including the three most effective epitope prediction softwares available online: Artificial Neural Network based B‑cell Epitope Prediction (ABCpred), B‑cell Epitope Prediction (BepiPred) and Linear B‑cell Epitope Prediction (LBtope). A total of 24 strains of Euro‑Asiatic AIV‑H7 that had been associated with a serious poultry pandemic or had infected humans in the past 30 years were selected to identify the conserved regions of HA. Sequences were obtained from the National Center for Biotechnology Information and Global Initiative on Sharing Avian Influenza Data databases. Using a combination of software prediction and sequence comparisons, the conserved epitopes of AIV‑H7 were predicted and clarified. A total of five conserved epitopes [amino acids (aa) 37‑52, 131‑142, 215‑234, 465‑484 and 487‑505] with a suitable length, high antigenicity and minimal variation were predicted and confirmed. Each obtained a score of >0.80 in ABCpred, 60% in LBtope and a level of 0.35 in Bepipred. In addition, a representative amino acid change (glutamine235‑to‑leucine235) in the HA protein of the 2013 AIV‑H7N9 was discovered. The strategy adopted in the present study may have profound implications on the rapid diagnosis and control of infectious disease caused by H7N9 viruses, as well as by other virulent viruses, such as the Ebola virus.

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1	Klimov A, Prösch S, Schäfer J and Bucher D: Subtype H7 influenza viruses: Comparative antigenic and molecular analysis of the HA-, M-, and NS-genes. Arch Virol. 122:143–161. 1992. View Article : Google Scholar : PubMed/NCBI
2	Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, et al: Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA. 101:1356–1361. 2004. View Article : Google Scholar : PubMed/NCBI
3	World Health Organization, . Human infection with avian influenza A (H7N9) virus - update. http://www.who.int/csr/don/2014_01_20/en/May 1–2014
4	Sun Y, Shen Y and Lu H: Discovery process, clinical characteristics, and treatment of patients infected with avian influenza virus (H7N9) in Shanghai. Chin Med J (Engl). 127:185–186. 2014.PubMed/NCBI
5	Li YJ, Jiao XA, Pan ZM, Sun L, Wang CB, Zhang SH, Sun QY and Liu XF: Development and characterization of monoclonal antibodies against H7 hemagglutinin of avian influenza virus. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 23:953–955. 2007.(In Chinese). PubMed/NCBI
6	Zhao B, Zhang X, Zhu W, Teng Z, Yu X, Gao Y, Wu D, Pei E, Yuan Z, Yang L, et al: Novel avian influenza A(H7N9) virus in tree sparrow, Shanghai, China, 2013. Emerg Infect Dis. 20:850–853. 2014. View Article : Google Scholar : PubMed/NCBI
7	Russell RJ, Kerry PS, Stevens DJ, Steinhauer DA, Martin SR, Gamblin SJ and Skehel JJ: Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion. Proc Natl Acad Sci USA. 105:17736–17741. 2008. View Article : Google Scholar : PubMed/NCBI
8	Wang Y, Dai Z, Cheng H, Liu Z, Pan Z, Deng W, Gao T, Li X, Yao Y, Ren J and Xue Y: Towards a better understanding of the novel avian-origin H7N9 influenza A virus in China. Sci Rep. 3:23182013.PubMed/NCBI
9	Barlow DJ, Edwards MS and Thornton JM: Continuous and discontinuous protein antigenic determinants. Nature. 322:747–748. 1986. View Article : Google Scholar : PubMed/NCBI
10	Evans MC: Recent advances in immunoinformatics: Application of in silico tools to drug development. Curr Opin Drug Discov Devel. 11:233–241. 2008.PubMed/NCBI
11	Van Regenmortel MH: Synthetic peptides versus natural antigens in immunoassays. Ann Biol Clin (Paris). 51:39–41. 1993.PubMed/NCBI
12	Saha S and Raghava GP: Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins. 65:40–48. 2006. View Article : Google Scholar : PubMed/NCBI
13	Zhu WF, Gao RB, Wang DY, Yang L, Zhu Y and Shu YL: A review of H7 subtype avain influenza virus. Bing Du Xue Bao. 29:245–249. 2013.(In Chinese). PubMed/NCBI
14	Larsen JE, Lund O and Nielsen M: Improved method for predicting linear B-cell epitopes. Immunome Res. 2:22006. View Article : Google Scholar : PubMed/NCBI
15	Parker JM, Guo D and Hodges RS: New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: Correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. Biochemistry. 25:5425–5432. 1986. View Article : Google Scholar : PubMed/NCBI
16	Singh H, Ansari HR and Raghava GP: Improved method for linear B-cell epitope prediction using antigen's primary sequence. PLoS One. 8:e622162013. View Article : Google Scholar : PubMed/NCBI
17	Xu R, de Vries RP, Zhu X, Nycholat CM, McBride R, Yu W, Paulson JC and Wilson IA: Preferential recognition of avian-like receptors in human influenza A H7N9 viruses. Science. 342:1230–1235. 2013. View Article : Google Scholar : PubMed/NCBI
18	Krchnák V, Mach O and Malý A: Computer prediction of B-cell determinants from protein amino acid sequences based on incidence of beta turns. Methods Enzymol. 178:586–611. 1989. View Article : Google Scholar : PubMed/NCBI
19	Pellequer JL, Westhof E and Van Regenmortel MH: Correlation between the location of antigenic sites and the prediction of turns in proteins. Immunol Lett. 36:83–99. 1993. View Article : Google Scholar : PubMed/NCBI
20	Dudek NL, Perlmutter P, Aguilar MI, Croft NP and Purcell AW: Epitope discovery and their use in peptide based vaccines. Curr Pharm Des. 16:3149–3157. 2010. View Article : Google Scholar : PubMed/NCBI
21	Bryson CJ, Jones TD and Baker MP: Prediction of immunogenicity of therapeutic proteins: Validity of computational tools. BioDrugs. 24:1–8. 2010. View Article : Google Scholar : PubMed/NCBI
22	De Groot AS, Sbai H, Aubin CS, McMurry J and Martin W: Immuno-informatics: Mining genomes for vaccine components. Immunol Cell Biol. 80:255–269. 2002. View Article : Google Scholar : PubMed/NCBI
23	Frikha-Gargouri O, Gdoura R, Znazen A, Gargouri B, Gargouri J, Rebai A and Hammami A: Evaluation of an in silico predicted specific and immunogenic antigen from the OmcB protein for the serodiagnosis of Chlamydia trachomatis infections. BMC Microbiol. 8:2172008. View Article : Google Scholar : PubMed/NCBI
24	Jones MS and Carter JM: Prediction of B-cell epitopes in listeriolysin O, a cholesterol dependent cytolysin secreted by listeria monocytogenes. Adv Bioinformatics. 2014:8716762014. View Article : Google Scholar : PubMed/NCBI
25	Maksimov P, Zerweck J, Maksimov A, Hotop A, Gross U, Pleyer U, Spekker K, Däubener W, Werdermann S, Niederstrasser O, et al: Peptide microarray analysis of in silico-predicted epitopes for serological diagnosis of Toxoplasma gondii infection in humans. Clin Vaccine Immunol. 19:865–874. 2012. View Article : Google Scholar : PubMed/NCBI
26	Saha S, Bhasin M and Raghava GP: Bcipep: A database of B-cell epitopes. BMC Genomics. 6:792005. View Article : Google Scholar : PubMed/NCBI
27	Karplus PA and Schulz GE: Prediction of chain flexibility in proteins. Naturwissenschaften. 72:212–213. 1985. View Article : Google Scholar
28	Emini EA, Hughes JV, Perlow DS and Boger J: Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol. 55:836–839. 1985.PubMed/NCBI
29	Costa JG, Faccendini PL, Sferco SJ, Lagier CM and Marcipar IS: Evaluation and comparison of the ability of online available prediction programs to predict true linear B-cell epitopes. Protein Pept Lett. 20:724–730. 2013. View Article : Google Scholar : PubMed/NCBI
30	Reimer U: Prediction of linear B-cell epitopes. Methods Mol Biol. 524:335–344. 2009. View Article : Google Scholar : PubMed/NCBI
31	Kageyama T, Fujisaki S, Takashita E, Xu H, Yamada S, Uchida Y, Neumann G, Saito T, Kawaoka Y and Tashiro M: Genetic analysis of novel avian A (H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill. 18:204532013.PubMed/NCBI
32	Liu D, Shi W, Shi Y, Wang D, Xiao H, Li W, Bi Y, Wu Y, Li X, Yan J, et al: Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: Phylogenetic, structural, and coalescent analyses. Lancet. 381:1926–1932. 2013. View Article : Google Scholar : PubMed/NCBI