Fig 1. Two models of the EV-A71 entry.

(A) The previous model suggested by Yamayoshi et al. [9,23]. SCARB2 is highly expressed on the cell surface. Surface SCARB2 binds to EV-A71 at the south rim of the canon [24] and initiates viral entry in endosomal vesicles. SCARB2 induces uncoating when the vesicle lumen becomes acidic. (B) Our new model. SCARB2 is absent from the cell surface. A non-SCARB2 receptor mediates EV-A71 attachment, most likely interacting with the viral five-fold vertex [20,21]. Virus is internalized and transported through the endosomal system, meeting SCARB2 within late endosomes or lysosomes, where uncoating occurs.