Enterovirus 71 infection induced Aquaporin-4 depolarization by increasing matrix metalloproteinase-9 activity

Aquaporin-4 (AQP4) is the key water channel protein that regulates brain water homeostasis. Polarized expression of AQP4 on the astroglial endfeet facilitates its role in bi-directional brain water flux control. In the current study, we found that enterovirus 71 (EV71) infection induced depolarization of AQP4 in mouse brain, and demonstrated that β-dystroglycan (β-DG), the key component of dystrophin glycoprotein complex (DGC) that anchors AQP4 to the astroglial endfeet, was degraded upon infection. Elevated activity or expression of matrix metalloproteinase 9 (MMP9) upon infection was found in both mouse brains and patient cerebrospinal fluid (CSF) samples. Inhibiting MMP9 activity by SB-3CT rescued the decay of β-DG and reduced the depolarization of AQP4. Brain edema induced by viral infection was also ameliorated by SB-3CT treatment in mice.