Red blood cells (RBCs) are the most abundant cell type in the
bloodstream, serving for oxygen transport. Although RBCs have been
considered as possible vehicles of virus transmission to target cells,
the mechanism is much less well understood. Here, we showed that porcine
epidemic diarrhea virus (PEDV), a coronavirus that caused acute and
devastating intestinal disease in suckling piglets, could cause typical
diarrhea in newborn piglets through hijacking RBCs. Firstly, PEDV could
bind and internalize into neonatal RBCs through CD71 and
clathrin-mediated endocytosis, and maintain its viability for 12 h.
Subsequently, after autotransfusion with PEDV-loaded RBCs, PEDV could
infect and colonize intestinal epithelial cells, causing typical
diarrhea symptoms in newborn piglets. Moreover, PEDV-loaded RBCs could
transfer the virus to CD3+ T cells by formation conjugation structure.
PEDV could continue to hitchhike CD3+ T cells to reach intestine mucosa
and cause infection. Finally, PEDV-loaded RBCs were found in nasal
capillary after intranasal infection with PEDV. Further, higher oxygen
concentration was determined as a promoter of PEDV binding RBCs.
Therefore, nasal capillary was speculated to be the entry for PEDV
binding RBCs. Collectively, our studies illustrated the mechanism that
PEDV could cause intestine infection through hijacking RBCs, further
providing a novel insight into the role of RBCs in coronavirus
pathogenesis as potential cells for viral transmission.