EV-A71 infection induces pathogenesis in various organs in humanized mice. Four-week-old humanized mice were inoculated i.p. with or without EV-A71 (108 PFU/mouse). Representative photomicrographs of H&E staining of different organs among mock-infected mice (n = 5), EV-A71-infected surviving mice (n = 6), and moribund mice (n = 4) are shown. Pathological changes were detected mainly in the organs of the EV-A71-infected moribund mice. Note the presence of vacuolation (black arrow) and gliosis (blue arrow) in brain stem; polymorphonuclear meningitis (black arrow) at the membrane of cerebral cortex; vacuolation (black arrow), gliosis (blue arrow), and polymorphonuclear or mononuclear meningomyelitis in spinal cord (red arrow); diffuse interstitial polymorphonuclear cell infiltrate (black arrow) and focal intra-alveolar hemorrhage (blue arrow) in lung; and focal interstitial mononuclear cell infiltrate (black arrow) in muscle. Bars, 100 μm.