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. 2016 Oct;12(4):2439-2446.
doi: 10.3892/etm.2016.3636. Epub 2016 Aug 31.

Computational Approach for Predicting the Conserved B-cell Epitopes of Hemagglutinin H7 Subtype Influenza Virus

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Free PMC article

Computational Approach for Predicting the Conserved B-cell Epitopes of Hemagglutinin H7 Subtype Influenza Virus

Xiangyu Wang et al. Exp Ther Med. .
Free PMC article

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.

Keywords: H7-subtype; avian-origin influenza virus; bioinformatics; linear B-cell epitope.

Figures

Figure 1.
Figure 1.
Conserved regions of the epitopes predicted by three epitope prediction softwares. The accession numbers of HA proteins from 24 strains of Euro-Asiatic avian-origin influenza virus, H7 subtype are listed on the left. The scales on the top show the rank of amino acids within HA. The amino acids in the first line of the graph are the H7N9 reference sequence. Other sequences are presented as dots if they share the same amino acid as the reference sequence or as the one-letter symbols if the amino acids are altered. The black boxes denote the locations of the 11 potential epitopes. Grey shaded areas denote highly conserved sequences. The 235th amino acid is denoted by a short black line. HA, hemagglutinin.
Figure 2.
Figure 2.
BepiPred linear epitope prediction. The abscissa represents the rank of HA amino acids and the ordinate represents the scores of every residue. Yellow denotes a positive score for linear B-cell epitopes. The horizontal axis denotes the threshold of 0.350. The further amino acids lie above the threshold, the greater possibility they have of becoming linear epitopes. According to their locations and scores, 19 potential epitopes were selected.
Figure 3.
Figure 3.
LBtope linear epitope prediction. The diagram depicts the entire amino acid sequence of hemagglutinin. Box areas have a possibility of 81 to 100% of being the epitope. Underlined areas have a possibility of 61 to 80%. The remaining areas have a possibility of 0 to 20%. The area can be considered as an epitope only when the possibility exceeds 60%.
Figure 4.
Figure 4.
Venn diagram of epitopes detected by ABCPred, BepiPred and LBtope. Black dots represent epitopes predicted by the three software packages. Epitopes predicted by ABCPred, BepiPred and LBtope are scattered in every circle. The 11 epitopes that were detected by all three algorithms are in the center of the Venn diagram. The center area is divided into two parts by a short line; the five dots that lie above the line represent five conserved sequences among the predicted epitopes.
Figure 5.
Figure 5.
The three dimensional structure of the HA protein. HA consists of two subunits: Purple and dark blue regions represent the HA1 and HA2 subunits of the protein, respectively. Yellow bands denote the five conserved epitopes predicted by the three algorithms, including epitopes (A) 10, (B) 11, (C) 6, (D) 8 and (E) 9. The circles show the amplified conserved epitopes and their detailed structures. HA, hemagglutinin.

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