ATN-161 reduces virus proliferation in PHEV-infected mice by inhibiting the integrin α5β1-FAK signaling pathway

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.