Yan Longfei, Li Yanran, Qi Jiancheng, Ren Li, Zhou Xueke, Gou Liping, Zuo Zhicai
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China.
State Key Laboratory of Virology, Taikang Center for Life and Medical Sciences, College of Life Sciences, Wuhan University, Wuhan, China.
Front Microbiol. 2025 May 9;16:1567288. doi: 10.3389/fmicb.2025.1567288. eCollection 2025.
Infectious bovine rhinotracheitis virus (IBRV) and co-infection are commonly observed in the respiratory tract of cattle subjected to respiratory diseases. However, the potential effects of proteases from on the IBRV infection remain poorly understood. In this study, we investigated the role of recombinant serralysin-like protease D (rSPD) in modulating IBRV infection in Madin-Darby bovine kidney (MDBK) cells. Our findings demonstrate that rSPD enhances IBRV replication and exacerbates the cytopathic effects of the virus on MDBK cells. Quantification of IBRV gene copy numbers using fluorescence quantification PCR (FQ-PCR) revealed that rSPD promotes viral replication during the intracellular stage, without affecting viral adsorption, entry, or directly interacting with viral particles. The transcriptomic analysis further demonstrated that rSPD suppresses innate immune responses while amplifying inflammatory pathways in IBRV-infected MDBK cells. Gene Ontology (GO) and KEGG enrichment analysis identified significant enrichment of differentially expressed genes (DEGs) in key signaling pathways, including JAK-STAT, NOD-like receptor, Toll-like receptor, TNF, NF-κB, and MAPK pathways. Notably, rSPD downregulated genes associated with innate immunity, such as , , , , , , , , , , , and , suggesting that rSPD suppresses host antiviral defenses. Conversely, rSPD upregulated genes involved in inflammatory response, including , , , , , and , indicating that rSPD may exacerbate cellular damage and promote viral replication by inducing excessive inflammatory responses. These findings provide novel insights into the interplay between bacterial proteases and viral infections, highlighting the potential role of bacterial proteases in exacerbating viral pathogenesis and offering a foundation for further research into therapeutic strategies targeting bacterial-viral interactions.
传染性牛鼻气管炎病毒（IBRV）及其合并感染在患有呼吸道疾病的牛的呼吸道中很常见。然而，来自[未提及具体来源]的蛋白酶对IBRV感染的潜在影响仍知之甚少。在本研究中，我们调查了重组类解链酶蛋白酶D（rSPD）在调节Madin-Darby牛肾（MDBK）细胞中IBRV感染的作用。我们的研究结果表明，rSPD增强了IBRV的复制，并加剧了病毒对MDBK细胞的细胞病变效应。使用荧光定量PCR（FQ-PCR）对IBRV基因拷贝数进行定量分析表明，rSPD在细胞内阶段促进病毒复制，而不影响病毒吸附、进入或直接与病毒颗粒相互作用。转录组分析进一步表明，rSPD在IBRV感染的MDBK细胞中抑制先天性免疫反应，同时放大炎症途径。基因本体（GO）和KEGG富集分析确定了关键信号通路中差异表达基因（DEGs）的显著富集，包括JAK-STAT、NOD样受体、Toll样受体、TNF、NF-κB和MAPK通路。值得注意的是，rSPD下调了与先天性免疫相关的基因，如[多个未明确的基因名称]，这表明rSPD抑制宿主抗病毒防御。相反，rSPD上调了参与炎症反应的基因，包括[多个未明确的基因名称]，这表明rSPD可能通过诱导过度炎症反应加剧细胞损伤并促进病毒复制。这些发现为细菌蛋白酶与病毒感染之间的相互作用提供了新的见解，突出了细菌蛋白酶在加剧病毒发病机制中的潜在作用，并为进一步研究针对细菌-病毒相互作用的治疗策略奠定了基础。
