Zhang Liyuan, Liang Dongli, Tian Yu, Liang Jiaxin, Li Xiaoquan, Liu Cheng, Liang Jingjing, Luo Ting Rong, Li Xiaoning
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530004, China.
College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China.
Biomolecules. 2025 Jan 31;15(2):200. doi: 10.3390/biom15020200.
Classical swine fever (CSF) is an acute and often fatal disease caused by CSF virus (CSFV) infection. In the present study, we investigated the transcriptional profiles of peripheral blood mononuclear cells (PBMCs) in pigs infected with CSFV. The results revealed that CSFV inhibits IFNα/β production, but up-regulates the expression of signal transducer and activator of transcription 1 (STAT1); this result was verified in vitro. Interestingly, STAT1 is typically a downstream target of IFNα/β, raising the question of how CSFV can inhibit IFNα/β expression, yet up-regulate STAT1 expression. To explore this further, we observed that UV-treated CSFV induced STAT1 expression. Our results demonstrated that CSFV E, E1, and E2 could up-regulate STAT1 expression within the host cell cytoplasm and facilitate its translocation into the nucleus. The E, E1, and E2 proteins also separately induced the up-regulation of interleukin (IL)-10; IL-10 acts as the communicator connecting E, E1, and E2 proteins to STAT1, leading to the subsequent up-regulation, phosphorylation, and nuclear translocation of STAT1. Silencing of IL-10 down-regulated STAT1 expression. Finally, MX1 and OAS1 were identified as downstream targets of the IL-10-STAT1 pathway. In summary, a novel IL-10-STAT1 pathway independent of IFNα/β induced by CSFV E, E1, and E2 was identified in this study.
经典猪瘟（CSF）是由CSF病毒（CSFV）感染引起的一种急性且往往致命的疾病。在本研究中，我们调查了感染CSFV的猪外周血单核细胞（PBMC）的转录谱。结果显示，CSFV抑制IFNα/β的产生，但上调信号转导和转录激活因子1（STAT1）的表达；这一结果在体外得到了验证。有趣的是，STAT1通常是IFNα/β的下游靶点，这就引发了一个问题，即CSFV如何能够抑制IFNα/β的表达，却又上调STAT1的表达。为了进一步探究这一问题，我们观察到经紫外线处理的CSFV可诱导STAT1表达。我们的结果表明，CSFV的E、E1和E2蛋白可在宿主细胞质内上调STAT1的表达，并促进其向细胞核的转运。E、E1和E2蛋白还分别诱导白细胞介素（IL）-10的上调；IL-10作为连接E、E1和E2蛋白与STAT1的介质，导致随后STAT1的上调、磷酸化及核转运。沉默IL-10可下调STAT1的表达。最后，MX1和OAS1被确定为IL-10-STAT1通路的下游靶点。总之，本研究确定了一条由CSFV的E、E1和E2诱导的独立于IFNα/β的新型IL-10-STAT1通路。
