Human endothelial cell activation and apoptosis induced by enterovirus 71 infection.

Enterovirus 71 (EV71), a neurotropic virus, its infection is transmitted mainly by the oral-fecal route. However, it is unclear how EV71 is disseminated/spread from initial replication sites to the central nervous system. Since endothelial cells form the interface between blood and tissues throughout the body, it is likely that EV71 can infect and then exit endothelial cells to establish infection. In this study, human endothelial cells were examined for susceptibility to EV71 infection using human microvascular endothelial cell line (HMEC-1 cell). Immunofluorescence assay confirmed EV71 infection of HMEC-1. Viable viruses were cultured from both the culture supernatant and the cell lysate. Live but not UV-inactivated EV71 induced HMEC-1 to secrete IL-6, macrophage migration inhibition factor, and macrophage chemo-attractant protein 1, and to express toll-like receptor 4. In addition, EV71 decreased the viability and increased the apoptosis of HMEC-1 cells after 36-48 hr of infection. These results demonstrate that EV71 is able to infect, activate, and induce apoptosis of endothelial cells, which may play a role in the pathogenesis of EV71 infection. 2004 Wiley-Liss, Inc.