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Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs

BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T...

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Autores principales: Pluta, Aneta, Albritton, Lorraine M., Rola-Łuszczak, Marzena, Kuźmak, Jacek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759284/
https://www.ncbi.nlm.nih.gov/pubmed/29310678
http://dx.doi.org/10.1186/s12977-017-0383-0
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author Pluta, Aneta
Albritton, Lorraine M.
Rola-Łuszczak, Marzena
Kuźmak, Jacek
author_facet Pluta, Aneta
Albritton, Lorraine M.
Rola-Łuszczak, Marzena
Kuźmak, Jacek
author_sort Pluta, Aneta
collection PubMed
description BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T cell epitopes found in naturally infected animals. In this study, we aimed to determine global variation and conservation within gp51 in the context of developing an effective global BLV vaccine. RESULTS: A total of 256 sequences extracted from the NCBI database and collected in different parts of the world, were studied to identify conserved segments along the env gene sequences that encode the gp51 protein. Using the MEME server and the conserved DNA Region module for analysis within DnaSP, we identified six conserved segments, referred to as A–F, and five semi-conserved segments, referred to as G–K. The amino acid conservation ranged from 98.8 to 99.8% in conserved segments A to F, while segments G to K had 89.6–95.2% conserved amino acid sequence. Selection analysis of individual segments revealed that residues of conserved segments had undergone purifying selection, whereas, particular residues in the semi-conserved segments are currently undergoing positive selection, specifically at amino acid positions 48 in segment K, 74 in segment G, 82 in segment I, 133 and 142 in segment J, and residue 291 in segment H. Each of the codons for these six residues contain the most highly variable nucleotides within their respective semi-conserved segments. CONCLUSIONS: The data described here show that the consensus amino acid sequence constitutes a strong candidate from which a global vaccine can be derived for use in countries where eradication by culling is not economically feasible. The most conserved segments overlap with amino acids in known immunodeterminants, specifically in epitopes D–D′, E-E′, CD8+ T-cell epitopes, neutralizing domain 1 and CD4+ T-cell epitopes. Two of the segments reported here represent unique segments that do not overlap with previously identified antigenic determinants. We propose that evidence of positive selection in some residues of the semi-conserved segments suggests that their variation is involved in viral strategy to escape immune surveillance of the host. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-017-0383-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-57592842018-01-10 Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs Pluta, Aneta Albritton, Lorraine M. Rola-Łuszczak, Marzena Kuźmak, Jacek Retrovirology Research BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T cell epitopes found in naturally infected animals. In this study, we aimed to determine global variation and conservation within gp51 in the context of developing an effective global BLV vaccine. RESULTS: A total of 256 sequences extracted from the NCBI database and collected in different parts of the world, were studied to identify conserved segments along the env gene sequences that encode the gp51 protein. Using the MEME server and the conserved DNA Region module for analysis within DnaSP, we identified six conserved segments, referred to as A–F, and five semi-conserved segments, referred to as G–K. The amino acid conservation ranged from 98.8 to 99.8% in conserved segments A to F, while segments G to K had 89.6–95.2% conserved amino acid sequence. Selection analysis of individual segments revealed that residues of conserved segments had undergone purifying selection, whereas, particular residues in the semi-conserved segments are currently undergoing positive selection, specifically at amino acid positions 48 in segment K, 74 in segment G, 82 in segment I, 133 and 142 in segment J, and residue 291 in segment H. Each of the codons for these six residues contain the most highly variable nucleotides within their respective semi-conserved segments. CONCLUSIONS: The data described here show that the consensus amino acid sequence constitutes a strong candidate from which a global vaccine can be derived for use in countries where eradication by culling is not economically feasible. The most conserved segments overlap with amino acids in known immunodeterminants, specifically in epitopes D–D′, E-E′, CD8+ T-cell epitopes, neutralizing domain 1 and CD4+ T-cell epitopes. Two of the segments reported here represent unique segments that do not overlap with previously identified antigenic determinants. We propose that evidence of positive selection in some residues of the semi-conserved segments suggests that their variation is involved in viral strategy to escape immune surveillance of the host. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-017-0383-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-08 /pmc/articles/PMC5759284/ /pubmed/29310678 http://dx.doi.org/10.1186/s12977-017-0383-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Pluta, Aneta
Albritton, Lorraine M.
Rola-Łuszczak, Marzena
Kuźmak, Jacek
Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
title Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
title_full Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
title_fullStr Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
title_full_unstemmed Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
title_short Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
title_sort computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759284/
https://www.ncbi.nlm.nih.gov/pubmed/29310678
http://dx.doi.org/10.1186/s12977-017-0383-0
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