Aquaporin‑4 deletion ameliorates enterovirus 71 infection in mice.

Aquaporin-4 (AQP4) is a major water channel of the central nervous system. The present study was designed to determine whether AQP4 deletion could ameliorate enterovirus (EV) 71 infection-induced hand, foot and mouth disease (HFMD) by inhibiting inflammation and apoptosis in mice. EV 71 strains were injected into neonatal BALB/c mice to induce HFMD. Western blotting and ELISA were used to measure the protein expression and cytokine levels. The levels of AQP4 mRNA and protein in the brain were increased in EV 71-infected mice, while the survival rate and health score were improved in AQP4-knockout (KO) mice with EV 71 infection. The EV 71 infection-induced increases of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, monocyte chemotactic protein-1, interferon (IFN)-alpha and IFN-gamma in plasma and brain were inhibited in AQP4-KO mice. AQP4 deletion reversed the decreased levels of Bcl2 and Bcl2/Bax, and the increased levels of Bax induced by EV 71 infection in the brain. These results demonstrated that AQP4 deletion ameliorated EV 71 induced-HFMD via inhibiting inflammation and apoptosis in mice.