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 se...

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Main Authors: Yingchen Wang, Zhe Zhang, Lei Shang, Hong Gao, Xiqiao Du, Falong Li, Ya Gao, Guiyun Qi, Weiyuan Guo, Zhangyi Qu, Tuo Dong
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.717047/full
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author Yingchen Wang
Zhe Zhang
Lei Shang
Hong Gao
Xiqiao Du
Xiqiao Du
Falong Li
Ya Gao
Guiyun Qi
Weiyuan Guo
Zhangyi Qu
Zhangyi Qu
Tuo Dong
author_facet Yingchen Wang
Zhe Zhang
Lei Shang
Hong Gao
Xiqiao Du
Xiqiao Du
Falong Li
Ya Gao
Guiyun Qi
Weiyuan Guo
Zhangyi Qu
Zhangyi Qu
Tuo Dong
author_sort Yingchen Wang
collection DOAJ
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.
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spelling doaj.art-a32cca786c3c4eee9bde4a2871a073452022-12-21T18:38:32ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-10-011210.3389/fmicb.2021.717047717047Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon ProteinYingchen Wang0Zhe Zhang1Lei Shang2Hong Gao3Xiqiao Du4Xiqiao Du5Falong Li6Ya Gao7Guiyun Qi8Weiyuan Guo9Zhangyi Qu10Zhangyi Qu11Tuo Dong12Department of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaHarbin Center for Disease Control and Prevention, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaThe Second Affiliated Hospital, Harbin Medical University, Harbin, ChinaThe Second Affiliated Hospital, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Natural Focus Disease Control, Institute of Environment-Associated Disease, Sino-Russia Joint Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Microbiology, Public Health College, Harbin Medical University, Harbin, ChinaAim: 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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.717047/fullhuman adenovirusprotein structureevolutionary tracecommon ancestor reconstructionserum immunity
spellingShingle Yingchen Wang
Zhe Zhang
Lei Shang
Hong Gao
Xiqiao Du
Xiqiao Du
Falong Li
Ya Gao
Guiyun Qi
Weiyuan Guo
Zhangyi Qu
Zhangyi Qu
Tuo Dong
Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein
Frontiers in Microbiology
human adenovirus
protein structure
evolutionary trace
common ancestor reconstruction
serum immunity
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 human adenovirus
protein structure
evolutionary trace
common ancestor reconstruction
serum immunity
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.717047/full
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