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The mechanisms of colostrum-mediated virus transmission are difficult to elucidate because of the absence of experimental animal models and the difficulties in tissue sample collection from mothers in the peripartum period. Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that has catastrophic impacts on the global pig industry. PEDV primarily infects neonatal piglets by multiple routes, especially 1- to 2-day-old neonatal piglets. Here, our epidemiological investigation and animal challenge experiments revealed that PEDV could be vertically transmitted from sows to neonatal piglets via colostrum, and CD3

Crossing the endothelium from the entry site and spreading in the bloodstream are crucial but obscure steps in the pathogenesis of many emerging viruses. Previous studies confirmed that porcine epidemic diarrhea virus (PEDV) caused intestinal infection by intranasal inoculation. However, the role of the nasal endothelial barrier in PEDV translocation remains unclear. Here, we demonstrated that PEDV infection causes nasal endothelial dysfunction to favor viral dissemination. Intranasal inoculation with PEDV compromised the integrity of endothelial cells (ECs) in nasal microvessels. The matrix metalloproteinase 7 (MMP-7) released from the PEDV-infected nasal epithelial cells (NECs) contributed to the destruction of endothelial integrity by degrading the tight junctions, rather than direct PEDV infection. Moreover, the proinflammatory cytokines released from PEDV-infected NECs activated ECs to upregulate ICAM-1 expression, which favored peripheral blood mononuclear cells (PBMCs) migration. PEDV could further exploit migrated cells to favor viral dissemination. Together, our results reveal the mechanism by which PEDV manipulates the endothelial dysfunction to favor viral dissemination and provide novel insights into how coronavirus interacts with the endothelium.

As the most abundant cell type in the blood, red blood cells (RBCs) are serving for transporting oxygen. However, the mechanism by which RBCs binding virus remains largely unknown. Here, we demonstrated that porcine epidemic diarrhea virus (PEDV), a kind of coronavirus, could hijack RBCs and cause typical diarrhea in neonatal piglets. In an epidemiology investigation of PEDV, the RBCs samples from diarrheic pigs in several pig farms were found to be PEDV-positive. PEDV could bind to neonatal RBCs through CD71 and clathrin-mediated endocytosis, and its viability was maintained for 12 h. PEDV-loaded RBCs could transfer the virus to CD3+ T cells by conjugation and reach the intestine mucosa, where it caused infection. Finally, a further animal challenge revealed that transfusing with PEDV-loaded RBCs could cause intestinal epithelial cells (IECs) infection and typical diarrhea symptom. Therefore, our studies illustrated the mechanism by which PEDV could cause intestinal infection through hijacking RBCs, further providing a novel insight into the role of RBCs as potential cells for viral transmission in coronavirus pathogenesis.

Porcine epidemic diarrhea virus (PEDV) causes acute and devastating intestinal disease in suckling piglets, resulting in a huge loss in the worldwide swine industry. Although several researches have reported that PEDV could cause viremia, the mechanism of how PEDV spread in the blood has been still unclear. Here, we showed PEDV could cause typical diarrhea in newborn piglets through hijacking red blood cells (RBCs). Firstly, PEDV could bind and internalize into neonatal RBCs through CD71 and clathrin-mediated endocytosis, and maintain its viability for 12 h. Subsequently, PEDV-loaded RBCs could transfer the virus to CD3+ T cells by formatting conjugation structure. PEDV could continue to hitchhike CD3+ T cells to reach intestine mucosa and cause infection. Moreover, after autotransfusion with PEDV-loaded RBCs, PEDV could infect and colonize intestinal epithelial cells, causing typical diarrhea symptoms in newborn piglets. Unintentionally, PEDV-loaded RBCs were found in nasal capillary after intranasal spraying with PEDV. Since oxygen partial pressure (pO2) and temperature of nasal cavity are different from other tissues, we further determined the higher pO2 was a promoting factor for PEDV binding RBCs. Therefore, the 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.