Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021, China.
Vet Microbiol. 2019 Jun;233:147-153. doi: 10.1016/j.vetmic.2019.04.029. Epub 2019 Apr 26.
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a typical neurotropic virus that can cause obvious nerve damage. Integrin α5β1 is a transmembrane macromolecular that closely related to neurological function. We recently demonstrated that integrin α5β1 plays a critical role in PHEV invasion in vitro. To determine the function and mechanism of integrin α5β1 in virus proliferation in vivo, we established a mouse model of PHEV infection. Integrin α5β1-FAK signaling pathway was activated in PHEV-infected mice by qPCR, Western blotting, and GST pull-down assays. Viral proliferation and integrin α5β1-FAK signaling pathway were significantly inhibited after intravenous injection of ATN-161, an integrin α5β1 inhibitor. Through a histological analysis, we found that ATN-161-treated mice only showed pathological changes in neuronal cytoplasmic swelling at 5 day post-infection. In summary, our results provide the first evidence that ATN-161 inhibits the proliferation of PHEV in mice and explores its underlying mechanisms of action.
猪传染性脑脊髓炎病毒（PHEV）是一种典型的嗜神经病毒，可引起明显的神经损伤。整合素α5β1 是一种与神经功能密切相关的跨膜大分子。我们最近的研究表明，整合素α5β1 在 PHEV 的体外入侵中起着关键作用。为了确定整合素α5β1 在体内病毒增殖中的功能和机制，我们建立了 PHEV 感染的小鼠模型。通过 qPCR、Western blot 和 GST 下拉实验，我们发现 PHEV 感染的小鼠中整合素α5β1-FAK 信号通路被激活。静脉注射整合素α5β1 抑制剂 ATN-161 后，病毒增殖和整合素α5β1-FAK 信号通路明显受到抑制。通过组织学分析，我们发现 ATN-161 处理的小鼠在感染后 5 天仅表现出神经元细胞质肿胀的病理变化。总之，我们的研究结果首次提供了 ATN-161 抑制 PHEV 在小鼠体内增殖的证据，并探讨了其作用机制。
