High expression of vascular endothelial growth factor in EV71-infected patients does not originate from EV71-infected cells

Background: Enterovirus (EV) 71 is an important pathogen causing death in children under 5 years of age worldwide. However, the core pathogenesis remains elusive. We reveal that the protein expression level of vascular endothelial growth factor (VEGF) in EV71 patients was 2-fold higher than in normal controls. However, the origin of VEGF in EV71-infected patients remains unclear. Methods: VEGF mRNA and protein expression in four EV71-infected cell lines was evaluated by RT-PCR, ELISA and Western blotting. Results: We found that only mRNA expression of VEGF was increased in the infected cells. Intra- and extracellular VEGF protein expression was decreased or unchanged in the four infected cell lines compared with the uninfected and inactivated EV71-infected cells. Conclusions: Our data reveal that EV71 infection of four human cell lines induced VEGF mRNA expression but did not induce VEGF protein expression in the infected cells. Therefore, the increased VEGF protein expression in EV71-infected patients may be due to the influence of surrounding non-infected cells following stimulation of proinflammatory cytokines secreted from the infected cells.