Journal
VETERINARY MICROBIOLOGY
Volume 233, Issue -, Pages 147-153Publisher
ELSEVIER
DOI: 10.1016/j.vetmic.2019.04.029
Keywords
Porcine hemagglutinating encephalomyelitis; virus; Integrin alpha 5 beta 1; FAK; ATN-161
Categories
Funding
- National Key Research and Development Program of China [2016YFD0500102]
- National Natural Science Foundation of China [31872446, 31772704, 31672519, 31602018]
- Scientific and Technological Project of Jilin Province [20180101270JC, 20170204033NY]
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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.
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