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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Frontiers Media S.A.
2021
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oai:doaj.org-article:3dc0aaf604fa4c408014eefaf33bc9f62021-12-01T23:20:42ZDevelopment of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 41664-302X10.3389/fmicb.2021.780978https://doaj.org/article/3dc0aaf604fa4c408014eefaf33bc9f62021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.780978/fullhttps://doaj.org/toc/1664-302XSevere 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.Qing PanYu ZhangAijing LiuHongyu CuiYulong GaoXiaole QiChangjun LiuYanping ZhangKai LiLi GaoXiaomei WangXiaomei WangFrontiers Media S.A.articleFAdV-4vaccine vectorHHSnon-essential regionsIBDVMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021) |
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FAdV-4 vaccine vector HHS non-essential regions IBDV Microbiology QR1-502 |
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FAdV-4 vaccine vector HHS non-essential regions IBDV Microbiology QR1-502 Qing Pan Yu Zhang Aijing Liu Hongyu Cui Yulong Gao Xiaole Qi Changjun Liu Yanping Zhang Kai Li Li Gao Xiaomei Wang Xiaomei Wang Development of a Novel Avian Vaccine Vector Derived From the Emerging Fowl Adenovirus 4 |
| 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. |
| format |
article |
| author |
Qing Pan Yu Zhang Aijing Liu Hongyu Cui Yulong Gao Xiaole Qi Changjun Liu Yanping Zhang Kai Li Li Gao Xiaomei Wang Xiaomei Wang |
| author_facet |
Qing Pan Yu Zhang Aijing Liu Hongyu Cui Yulong Gao Xiaole Qi Changjun Liu Yanping Zhang Kai Li Li Gao Xiaomei Wang Xiaomei Wang |
| author_sort |
Qing Pan |
| title |
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_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_sort |
development of a novel avian vaccine vector derived from the emerging fowl adenovirus 4 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/3dc0aaf604fa4c408014eefaf33bc9f6 |
| work_keys_str_mv |
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| _version_ |
1718403978715201536 |