Villalba Melina, Pérez Valeria, Herrera Laura, Stepke Cristopher, Maldonado Nicolas, Fredericksen Fernanda, Yáñez Alejandro, Olavarría Víctor H
Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile; Interdisciplinary Center for Aquaculture Research (INCAR), Universidad Austral de Chile, Valdivia, Chile.
Vet Immunol Immunopathol. 2017 Dec;193-194:10-17. doi: 10.1016/j.vetimm.2017.09.009. Epub 2017 Oct 9.
The pathogenic infectious pancreatic necrosis virus (IPNV) causes high economic losses in fish farming. This virus can modulate several cellular processes during infection, but little is known about the infection mechanism. To investigate gene activation in response to IPNV, CHSE/F and SHK-1 cell line were infected with a cytopathic Sp field isolate of IPNV, and the expression profiles of proinflammatory, antiviral cytokine, and extracellular matrix markers were analyzed. IPNV induced the production of perlecan, fibulin-1, matrix metalloproteinase-2, 14-3-3β, interleukin-1β, Mx1, and interferon regulatory factors-1, -3, and -9. Interestingly, IPNV-mediated activity was blocked by pharmacological inhibitors of the NF-κB signaling pathway. These results, together with in silico analyses showing the presence of several regulatory consensus-target motifs, suggest that IPNV regulates gene expressions in fish through the activation of several key transcription factors. Collectively, these data indicate that IPNV is a viral regulator of expression for extracellular-matrix and immune markers, even during early infection. Finally, this is the first report in fish to find IPNV modulating the activation of interleukin-1β production primarily through the NF-κB pathway.
致病性传染性胰腺坏死病毒(IPNV)给养鱼业造成了巨大经济损失。该病毒在感染过程中可调节多种细胞过程,但对其感染机制却知之甚少。为了研究IPNV感染后基因的激活情况,用IPNV的一个具有细胞病变效应的Sp田间分离株感染CHSE/F和SHK-1细胞系,并分析促炎、抗病毒细胞因子及细胞外基质标志物的表达谱。IPNV诱导了基底膜聚糖、纤连蛋白-1、基质金属蛋白酶-2、14-3-3β、白细胞介素-1β、Mx1以及干扰素调节因子-1、-3和-9的产生。有趣的是,IPNV介导的活性被NF-κB信号通路的药理学抑制剂所阻断。这些结果,连同计算机分析显示存在多个调控共有靶基序,表明IPNV通过激活几个关键转录因子来调节鱼类的基因表达。总体而言,这些数据表明,即使在早期感染期间,IPNV也是细胞外基质和免疫标志物表达的病毒调节因子。最后,这是在鱼类中首次发现IPNV主要通过NF-κB途径调节白细胞介素-1β产生的激活的报告。