A new anti-influenza animal model for Traditional Chinese Medicine, restraint stress induces influenza susceptibility by regulating mitochondrial antiviral signaling pathway

There are many kinds of Chinese patent medicine used to fight against influenza efficiently in clinical practice. However, little experimental data confirmed the anti-influenza the activities since non-suitable animal model and in vitro antiviral experiments. This paradox can be explained by host factors are important in the patho- genesis and outcome of influenza infection. Accordingly, we set up a mouse model by using restraint stress plus vi- ral infection, which is more conducive to simulate the clinical features of susceptible population and evaluate the activities of Chinese herbal medicine. Our results demonstrated that stress-induced corticosterone （CORT） , a stres- sor sensor, increased the morbidity and the mortality of virus infected mice loaded with restraint stress. CORT also increased expression of Mfn2, and accordingly decreased mitochondrial antiviral signaling （MAVS） aggregates in the host cells. Mfn2 overexpression increased NP and decreased IFN-β and IFITM3 protein expressions in influenza virus infected A549 cells. These findings suggested that the mechanism of restraint stress increased the susceptibili- ty due to CORT induces activation of Mfn2 mediated MAVS pathway.