ATN-161 reduces virus proliferation in PHEV-infected mice by inhibiting the integrin α5β1-FAK signaling pathway
ATN-161 reduces virus proliferation in PHEV-infected mice by inhibiting the integrin α5β1-FAK signaling pathway
复制标题
ATN-161 通过抑制整合素 α 5 β 1-FAK 信号通路减少 PHEV 感染小鼠的病毒增殖
DOI：
10.1016/j.vetmic.2019.04.029
复制
发表时间：
2019-06-01
影响因子：
3.3
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Lv, Xiaoling;Li, Zi;Gao, Feng
猪血凝性脑脊髓炎病毒(PHEV)是一种典型的嗜神经病毒，可引起明显的神经损害。整合素α5β1是一种与神经功能密切相关的跨膜大分子。我们最近证实整合素α5β1在PHEV体外侵袭中起关键作用。为了确定整合素α5β1在体内病毒增殖中的作用和机制，我们建立了PHEV感染的小鼠模型。在PHEV感染的小鼠中，整合素α5β1-FAK信号通路通过qPCR、Western blotting和GST下拉实验被激活。静脉注射整合素α5β1抑制剂ATN-161后，病毒增殖和整合素α5β1-FAK信号通路受到明显抑制。通过组织学分析，我们发现ATN-161处理的小鼠在感染后第5天才出现神经细胞胞浆肿胀的病理变化。综上所述，我们的结果提供了ATN-161抑制小鼠体内PHEV增殖的第一个证据，并探索了其潜在的作用机制。
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a typical neurotropic virus that can cause obvious nerve damage. Integrin alpha 5 beta 1 is a transmembrane macromolecular that closely related to neurological function. We recently demonstrated that integrin alpha 5 beta 1 plays a critical role in PHEV invasion in vitro. To determine the function and mechanism of integrin alpha 5 beta 1 in virus proliferation in vivo, we established a mouse model of PHEV infection. Integrin alpha 5 beta 1-FAK signaling pathway was activated in PHEV-infected mice by qPCR, Western blotting, and GST pull-down assays. Viral proliferation and integrin alpha 5 beta 1-FAK signaling pathway were significantly inhibited after intravenous injection of ATN-161, an integrin alpha 5 beta 1 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.