The study of EV71–host interplay is of importance for understanding viral infection and could benefit design strategies for prevention and therapy [37, 38]. Here, we show that DCs can transfer surface-bound EV71 to susceptible RD cells for robust infection, although no apparent viral replication in MDDCs was observed. The surface-expressing viral attachment factor DC-SIGN mediates EV71 binding and transfer.
DC-SIGN has been shown to be hijacked by several types of viruses for mediating capture and transmission [27, 28]. DC-SIGN can bind high-mannose-containing glycoproteins, such as HIV-1 gp120 and HCV E1 and E2 glycoprotein . DC-SIGN has been demonstrated to mediate partially EV71 binding to MDDCs , although the specific molecular basis of EV71 that accounts for binding to DC-SIGN needs to be further clarified.
DC-SIGN also can mediate viral endocytosis , and here, we observed EV71 internalization into MDDCs. Whether DC-SIGN plays a role in viral endocytosis needs to be further examined. A recent publication reported that both SCARB2 and PSGL-1 could bind EV71 viruses when these receptors were stably expressed on mouse L929 cells, and SCARB2 efficiently mediated viral internalization and uncoating . Clathrin-mediated endocytosis has been reported to act as an entry pathway for EV71 infection of susceptible RD cells . However, despite EV71 binding and endocytosis into MDDCs, no apparent viral infection was observed, and these internalized viruses were rapidly degraded. The contradiction between EV71 infection of MDDCs in the present and other studies may be due to different viral strains and infection situations .
EV71 replication causes apoptosis of a wide range of host cells, such as human glioblastoma cells, microvascular endothelial cell line, neural cells, RD cells, Vero cells, HeLa cells, and Jurkat T cells [29–33, 35, 36]. Similarly, the replication of transferred EV71 mediated by MDDCs also induced RD cell death in our study, while MDDC viability was not greatly affected. The cell selectivity might have been due to the lower susceptibility of MDDCs for EV71 replication. The pathways of EV71-induced apoptosis remain elusive [34, 36, 41]. EV71 infection can induce Fas ligand expression on Jurkat T cells  and trigger activation of caspase 3 and 8 and poly (ADP-ribose) polymerases in RD cells . Viral protein synthesis appears to be required for inducing cell apoptosis, and expression of 2A and 3C proteases is associated with induction of apoptosis [31, 32]. Blocking with specific antibodies such as DC-SIGN prior to EV71 infection could provide an alternative approach for blocking viral replication and viremia by reducing viral binding and transmission mediated by MDDCs.
Overall, although the in vivo investigation needs to be further clarified, our in vitro findings hint at the potential role of DCs in EV71 primary infection and may benefit the search for new ways to prevent viruses from initial infection.