Key Laboratory of Animal Epidemiology of Chinese Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China; China Institute of Veterinary Drug Control, Beijing, 100081, PR China.
China Institute of Veterinary Drug Control, Beijing, 100081, PR China.
Vet Microbiol. 2021 Apr;255:109026. doi: 10.1016/j.vetmic.2021.109026. Epub 2021 Mar 3.
Fowl adenovirus serotype 4 (FAdV-4) is recognized as an economically important pathogen for the poultry industry worldwide. FAdV-4 infection causes a metabolic disturbance of hepatocytes, leading to hydropericardium-hepatitis syndrome (HHS) in poultry. However, the metabolic response of hepatocytes to FAdV-4 infection remains poorly investigated. Here, a tandem mass tag (TMT)-based approach was first used to quantitatively identify differentially expressed proteins (DEPs) in leghorn male hepatoma (LMH) cells infected with the virulent FAdV-4 strain GY. We identified 666 DEPs associated with many biological processes and pathways, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Functional enrichment analysis revealed that three pathways, including metabolism-related signaling pathways, apoptosis, and autophagy responses, were enriched during FAdV-4 infection. Moreover, excessive induction of metabolism-related signaling pathways by FAdV-4 infection might be associated with HHS induced by the virus. Meanwhile, among the proteins in these pathways, RRM2, SAE1, AEN, and RAD50 were verified through western blotting to be markedly altered in FAdV-4-infected LMH cells. Notably, overexpression of SAE1 inhibited the replication of FAdV-4 in vitro, whereas silencing of SAE1 expression promoted the replication of the virus. Collectively, our findings show for the first time that SAE1 is a host cellular protein that plays roles in regulating the life cycle of FAdV-4.
禽腺病毒血清型 4（FAdV-4）被认为是全球家禽养殖业中一种具有重要经济意义的病原体。FAdV-4 感染会导致肝细胞代谢紊乱，从而引发家禽的包涵体肝炎-心包积水综合征（HHS）。然而，肝细胞对 FAdV-4 感染的代谢反应仍未得到充分研究。在这里，我们首次使用串联质量标签（TMT）方法定量鉴定了感染强毒 FAdV-4 株 GY 的莱航雄性鸡胚肝细胞（LMH）中的差异表达蛋白（DEPs）。根据基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，我们鉴定出与许多生物学过程和通路相关的 666 个 DEPs。功能富集分析表明，在 FAdV-4 感染过程中，有三个通路，包括代谢相关信号通路、细胞凋亡和自噬反应，被富集。此外，FAdV-4 感染过度诱导代谢相关信号通路可能与该病毒引起的 HHS 有关。同时，在这些通路中的蛋白质中，RRM2、SAE1、AEN 和 RAD50 通过 Western blot 验证在 FAdV-4 感染的 LMH 细胞中明显改变。值得注意的是，SAE1 的过表达抑制了 FAdV-4 在体外的复制，而 SAE1 表达的沉默促进了病毒的复制。总的来说，我们的研究结果首次表明，SAE1 是一种宿主细胞蛋白，在调节 FAdV-4 的生命周期中发挥作用。
