Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication

Fowl adenovirus serotype 4 (FAdV-4), a member of the family Adenoviridae and the genus Aviadenovirus, is responsible for a significant number of emerging diseases that cause substantial economic losses in the poultry industry worldwide. The hexon protein plays a crucial role in inducing autophagy an...

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Main Authors: Xiaojun Zhang, Xueping Wang, Yina Zhao, Shifan Li, Xingang Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1562872/full
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author Xiaojun Zhang
Xueping Wang
Yina Zhao
Shifan Li
Xingang Xu
author_facet Xiaojun Zhang
Xueping Wang
Yina Zhao
Shifan Li
Xingang Xu
author_sort Xiaojun Zhang
collection DOAJ
description Fowl adenovirus serotype 4 (FAdV-4), a member of the family Adenoviridae and the genus Aviadenovirus, is responsible for a significant number of emerging diseases that cause substantial economic losses in the poultry industry worldwide. The hexon protein plays a crucial role in inducing autophagy and apoptosis and promoting virus replication. Identifying host factors that interact with the hexon protein is essential for elucidating the pathogenesis of FAdV-4. In this study, tandem affinity purification followed by mass spectrometry (TAP/MS) was used to screen the interacting proteins of hexon in leghorn male hepatoma (LMH) cells for the first time. A total of 82 hexon-associated proteins were identified in LMH cells expressing hexon compared with cells expressing the empty vector (NC). Gene Ontology and Ingenuity Pathway Analysis provided functional annotations of the hexon-interacting proteins and revealed that these proteins were associated with multiple biological functions, including virus infection, the cell cycle, endocytosis and the phagosome. Western blot and coimmunoprecipitation validation tests revealed that randomly selected significant proteins (CCT5, CCT7, and HSP70) interact with hexon, and these results are consistent with those of TAP/MS. Among them, the overexpression of CCT5 inhibited virus replication, whereas blocking CCT5 increased virus replication. In conclusion, this study demonstrated the successful screening of host proteins interacting with the hexon protein. The findings of this study will lead to a better understanding of the molecular mechanisms of hexon, thus benefiting the development of effective antiviral strategies.
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spelling doaj-art-05d50077dd724e1d9e382f33d859d1d82025-08-20T03:19:23ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-06-011210.3389/fvets.2025.15628721562872Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replicationXiaojun Zhang0Xueping Wang1Yina Zhao2Shifan Li3Xingang Xu4College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Animal Science and Technology, Tarim University, Alaer, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaFowl adenovirus serotype 4 (FAdV-4), a member of the family Adenoviridae and the genus Aviadenovirus, is responsible for a significant number of emerging diseases that cause substantial economic losses in the poultry industry worldwide. The hexon protein plays a crucial role in inducing autophagy and apoptosis and promoting virus replication. Identifying host factors that interact with the hexon protein is essential for elucidating the pathogenesis of FAdV-4. In this study, tandem affinity purification followed by mass spectrometry (TAP/MS) was used to screen the interacting proteins of hexon in leghorn male hepatoma (LMH) cells for the first time. A total of 82 hexon-associated proteins were identified in LMH cells expressing hexon compared with cells expressing the empty vector (NC). Gene Ontology and Ingenuity Pathway Analysis provided functional annotations of the hexon-interacting proteins and revealed that these proteins were associated with multiple biological functions, including virus infection, the cell cycle, endocytosis and the phagosome. Western blot and coimmunoprecipitation validation tests revealed that randomly selected significant proteins (CCT5, CCT7, and HSP70) interact with hexon, and these results are consistent with those of TAP/MS. Among them, the overexpression of CCT5 inhibited virus replication, whereas blocking CCT5 increased virus replication. In conclusion, this study demonstrated the successful screening of host proteins interacting with the hexon protein. The findings of this study will lead to a better understanding of the molecular mechanisms of hexon, thus benefiting the development of effective antiviral strategies.https://www.frontiersin.org/articles/10.3389/fvets.2025.1562872/fullfowl adenovirus serotype 4hexon proteinCCT5tandem affinity purificationbioinformatics analysisinteraction protein
spellingShingle Xiaojun Zhang
Xueping Wang
Yina Zhao
Shifan Li
Xingang Xu
Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication
Frontiers in Veterinary Science
fowl adenovirus serotype 4
hexon protein
CCT5
tandem affinity purification
bioinformatics analysis
interaction protein
title Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication
title_full Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication
title_fullStr Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication
title_full_unstemmed Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication
title_short Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication
title_sort unveiling the role of hexon associated host proteins in fowl adenovirus serotype 4 replication
topic fowl adenovirus serotype 4
hexon protein
CCT5
tandem affinity purification
bioinformatics analysis
interaction protein
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1562872/full
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AT xuepingwang unveilingtheroleofhexonassociatedhostproteinsinfowladenovirusserotype4replication
AT yinazhao unveilingtheroleofhexonassociatedhostproteinsinfowladenovirusserotype4replication
AT shifanli unveilingtheroleofhexonassociatedhostproteinsinfowladenovirusserotype4replication
AT xingangxu unveilingtheroleofhexonassociatedhostproteinsinfowladenovirusserotype4replication