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Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4

Severe hepatitis-hydropericardium syndrome (HHS) associated with a novel viral genotype, fowl adenovirus 4 (FAdV-4), has emerged and widely spread in China since 2015, causing severe economic losses to the poultry industry. We previously reported that the hexon gene is responsible for pathogenicity...

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Autores principales: Pan, Qing, Zhang, Yu, Liu, Aijing, Cui, Hongyu, Gao, Yulong, Qi, Xiaole, Liu, Changjun, Zhang, Yanping, Li, Kai, Gao, Li, Wang, Xiaomei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671827/
https://www.ncbi.nlm.nih.gov/pubmed/34925286
http://dx.doi.org/10.3389/fmicb.2021.780978
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author Pan, Qing
Zhang, Yu
Liu, Aijing
Cui, Hongyu
Gao, Yulong
Qi, Xiaole
Liu, Changjun
Zhang, Yanping
Li, Kai
Gao, Li
Wang, Xiaomei
author_facet Pan, Qing
Zhang, Yu
Liu, Aijing
Cui, Hongyu
Gao, Yulong
Qi, Xiaole
Liu, Changjun
Zhang, Yanping
Li, Kai
Gao, Li
Wang, Xiaomei
author_sort Pan, Qing
collection PubMed
description Severe hepatitis-hydropericardium syndrome (HHS) associated with a novel viral genotype, fowl adenovirus 4 (FAdV-4), has emerged and widely spread in China since 2015, causing severe economic losses to the poultry industry. We previously reported that the hexon gene is responsible for pathogenicity and obtained a non-pathogenic hexon-replacement rHN20 strain; however, the lack of information about the non-essential regions for virus replication limits the development of a FAdV-4 vector. This study first established an enhanced green fluorescent protein (EGFP)-indicator virus based on the FAdV-4 reverse genetic technique, effective for batch operations in the virus genome. Based on this, 10 open reading frames (ORFs) at the left end and 13 ORFs at the right end of the novel FAdV-4 genome were deleted separately and identified as non-essential genes for viral replication, providing preliminary insertion sites for foreign genes. To further improve its feasibility as a vaccine vector, seven combinations of ORFs were successfully replaced with EGFP without affecting the immunogenicity of the vector backbone. Finally, a recombinant rHN20-vvIBDV-VP2 strain, expressing the VP2 protein of very virulent infectious bursa disease virus (vvIBDV), was rescued and showed complete protection against FAdV-4 and vvIBDV. Thus, the novel FAdV-4 vector could provide sufficient protection for HHS and efficient exogenous gene delivery. Overall, our findings systemically identified 23 non-essential ORFs for FAdV-4 replication and seven foreign gene insertion regions, providing valuable information for an in-depth understanding of the novel FAdV-4 pathogenesis and development of multivalent vaccines.
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spelling pubmed-86718272021-12-16 Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4 Pan, Qing Zhang, Yu Liu, Aijing Cui, Hongyu Gao, Yulong Qi, Xiaole Liu, Changjun Zhang, Yanping Li, Kai Gao, Li Wang, Xiaomei Front Microbiol Microbiology Severe hepatitis-hydropericardium syndrome (HHS) associated with a novel viral genotype, fowl adenovirus 4 (FAdV-4), has emerged and widely spread in China since 2015, causing severe economic losses to the poultry industry. We previously reported that the hexon gene is responsible for pathogenicity and obtained a non-pathogenic hexon-replacement rHN20 strain; however, the lack of information about the non-essential regions for virus replication limits the development of a FAdV-4 vector. This study first established an enhanced green fluorescent protein (EGFP)-indicator virus based on the FAdV-4 reverse genetic technique, effective for batch operations in the virus genome. Based on this, 10 open reading frames (ORFs) at the left end and 13 ORFs at the right end of the novel FAdV-4 genome were deleted separately and identified as non-essential genes for viral replication, providing preliminary insertion sites for foreign genes. To further improve its feasibility as a vaccine vector, seven combinations of ORFs were successfully replaced with EGFP without affecting the immunogenicity of the vector backbone. Finally, a recombinant rHN20-vvIBDV-VP2 strain, expressing the VP2 protein of very virulent infectious bursa disease virus (vvIBDV), was rescued and showed complete protection against FAdV-4 and vvIBDV. Thus, the novel FAdV-4 vector could provide sufficient protection for HHS and efficient exogenous gene delivery. Overall, our findings systemically identified 23 non-essential ORFs for FAdV-4 replication and seven foreign gene insertion regions, providing valuable information for an in-depth understanding of the novel FAdV-4 pathogenesis and development of multivalent vaccines. Frontiers Media S.A. 2021-12-01 /pmc/articles/PMC8671827/ /pubmed/34925286 http://dx.doi.org/10.3389/fmicb.2021.780978 Text en Copyright © 2021 Pan, Zhang, Liu, Cui, Gao, Qi, Liu, Zhang, Li, Gao and Wang. 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
Pan, Qing
Zhang, Yu
Liu, Aijing
Cui, Hongyu
Gao, Yulong
Qi, Xiaole
Liu, Changjun
Zhang, Yanping
Li, Kai
Gao, Li
Wang, Xiaomei
Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4
title Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4
title_full Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4
title_fullStr Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4
title_full_unstemmed Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4
title_short Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4
title_sort development of a novel avian vaccine vector derived from the emerging fowl adenovirus 4
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671827/
https://www.ncbi.nlm.nih.gov/pubmed/34925286
http://dx.doi.org/10.3389/fmicb.2021.780978
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