Figure 6: LNA antagomiR-146a treatment improves survival and restores IFN production in EV71 mouse model.

(a) LNA antagomiR-146a treatment improves survival rate. Wild-type mice were treated with LNA antagomiR-146a (1.2 mg kg⁻¹) before or after mEV71 infection and monitored daily for survival rate. * represents the comparison between the 2 × 10⁸ PFU/anti-146a 1 d.p.i. group and the 2 × 10⁸ PFU/anti-NC group; ** represents the comparison between the 2 × 10⁸ PFU/anti-146a 0 d.p.i. group and the 2 × 10⁸ PFU/anti-NC group. (b) The increase of miR-146a expression was neutralized in EV71-infected mice by injection with LNA antagomiR-146a (n=3). (c) Suppression of IRAK1 and TRAF6 was restored by LNA antagomiR-146a injection. IFNβ (n=3) (d) and IRF1 and IFIT1 (n=3) (e) expressions were induced in EV71-infected wild-type mice injected with LNA antagomiR-146a as measured by real-time RT–PCR (mouse tissue samples pooling, n=4). (f) Anti-IFNα/β antibodies eliminated antagomiR-146a-mediated improved survival. LNA antagomiR-146a and anti-IFNα/β antibodies were sequentially injected before virus infection and the mouse survival was recorded daily. * represents the comparison between the 2 × 10⁸ PFU/anti-146a group and the 2 × 10⁸ PFU/anti-NC group; ** represents the comparison between the 2 × 10⁸ PFU/anti-146a group and the 2 × 10⁸ PFU/anti-146a/anti-IFNs group. The Kaplan–Meier method was used to estimate overall survival and the Log-rank test was performed to test the difference between survival curves.