【摘要】 禽腺病毒血清4型（FAdV-4）是鸡肝炎-心包积液综合征（HHS）的主要病原体，其非结构蛋白ORF22缺失毒株感染会导致病毒噬斑变小且在动物体内复制能力下降，但具体机制尚不明确。为了探究ORF22蛋白在FAdV-4感染过程中的作用，本研究以鸡肝癌细胞（LMH）为试验模型，利用转录组测序技术进行解析。结果显示，与对照组相比，ORF22过表达组共筛选到362个差异表达基因（DEGs）。其中，321个DEGs表达上调，41个DEGs表达下调。对这些差异表达基因进行GO分析发现，下调的DEGs主要与小分子代谢过程、膜区域、蛋白质结合相关，而上调的DEGs主要与细胞过程的调节、细胞外区域和信号受体结合相关。KEGG通路分析显示，DEGs主要富集在TGF-β信号通路、MAPK信号通路、钙离子信号通路、细胞因子-细胞因子受体相互作用等。此外，通过蛋白质相互作用网络分析发现，HSP90AA1、HSPA8、BAG3等多个关键蛋白位于整个网络中心。过表达ORF22显著降低了宿主细胞天然免疫相关蛋白cGAS、STING、TBK1的表达。综上所述，本研究揭示了ORF22蛋白在FAdV-4感染中与宿主细胞的相互作用，为解析FAdV-4致病机制提供了参考。更多还原

【Abstract】 Fowl adenovirus serotype 4(FAdV-4) is the primary pathogen causing Hepatitis-hydropericardium syndrome(HHS) in chickens. Infection with its non-structural protein ORF22 deletion strain leads to smaller viral plaques and reduced replication ability in animals. However, the exact mechanism remains unclear. To investigate the role of ORF22 protein in FAdV-4 infection, this study used Leghorn male hepatocellular(LMH) cells as an experimental model and resolved it using transcriptome sequencing technology. The findings demonstrated that, compared to the control group, 362 differentially expressed genes(DEGs) were identified in the ORF22 overexpression group, with 321 up-regulated and 41 down-regulated expression. GO analysis indicated that up-regulated DEGs were predominantly enriched in cellular process regulation, extracellular regions, and signaling receptor binding, whereas the down-regulated DEGs were primarily associated with membrane regions, protein binding, and small molecule metabolic processes. According to KEGG pathway analysis, DEGs were significantly enriched in TGF-β signaling pathway, MAPK signaling pathway, calcium signaling system, cytokine-cytokine receptor interaction, and so on. Furthermore, the protein-protein interaction network identified several important proteins, including HSP90 AA1, HSPA8, and BAG3, which were centrally positioned within the network. Notably, ORF22 overexpression markedly decreased the expression of innate immunity-related proteins cGAS, STING, and TBK1 in host cells. In summary, this study elucidates the interaction between ORF22 protein and host cells during FAdV-4 infection, providing valuable insights into the pathogenic mechanism of FAdV-4.更多还原