Cargando…
Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein
Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations. Methods: The s...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578728/ https://www.ncbi.nlm.nih.gov/pubmed/34777273 http://dx.doi.org/10.3389/fmicb.2021.717047 |
_version_ | 1784596295457964032 |
---|---|
author | Wang, Yingchen Zhang, Zhe Shang, Lei Gao, Hong Du, Xiqiao Li, Falong Gao, Ya Qi, Guiyun Guo, Weiyuan Qu, Zhangyi Dong, Tuo |
author_facet | Wang, Yingchen Zhang, Zhe Shang, Lei Gao, Hong Du, Xiqiao Li, Falong Gao, Ya Qi, Guiyun Guo, Weiyuan Qu, Zhangyi Dong, Tuo |
author_sort | Wang, Yingchen |
collection | PubMed |
description | Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations. Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples. Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults. Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors. |
format | Online Article Text |
id | pubmed-8578728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85787282021-11-11 Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein Wang, Yingchen Zhang, Zhe Shang, Lei Gao, Hong Du, Xiqiao Li, Falong Gao, Ya Qi, Guiyun Guo, Weiyuan Qu, Zhangyi Dong, Tuo Front Microbiol Microbiology Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations. Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples. Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults. Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8578728/ /pubmed/34777273 http://dx.doi.org/10.3389/fmicb.2021.717047 Text en Copyright © 2021 Wang, Zhang, Shang, Gao, Du, Li, Gao, Qi, Guo, Qu and Dong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Wang, Yingchen Zhang, Zhe Shang, Lei Gao, Hong Du, Xiqiao Li, Falong Gao, Ya Qi, Guiyun Guo, Weiyuan Qu, Zhangyi Dong, Tuo Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein |
title | Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein |
title_full | Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein |
title_fullStr | Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein |
title_full_unstemmed | Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein |
title_short | Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein |
title_sort | immunological study of reconstructed common ancestral sequence of adenovirus hexon protein |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578728/ https://www.ncbi.nlm.nih.gov/pubmed/34777273 http://dx.doi.org/10.3389/fmicb.2021.717047 |
work_keys_str_mv | AT wangyingchen immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT zhangzhe immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT shanglei immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT gaohong immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT duxiqiao immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT lifalong immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT gaoya immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT qiguiyun immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT guoweiyuan immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT quzhangyi immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein AT dongtuo immunologicalstudyofreconstructedcommonancestralsequenceofadenovirushexonprotein |