Abstract
Porcine epidemic diarrhea virus (PEDV) can cause intestinal infection in neonatal piglets through the nasal cavity. A process in which CD3+ T cells carry PEDV plays a key role. However, the modes through which PEDV bridles CD3+ T cells as a vehicle for migration to the intestinal epithelium have not been clarified. In this study, we first demonstrated that PEDV could survive in blood-derived CD3+ T cells for several hours, depending on the multiplicity of infection. In addition, PEDV preferentially survived in CD4+ T cells over CD8+ T cells. Moreover, viral transmission was mediated by cell-to-cell contact between mesenteric lymph-node-derived CD3+ T cells, but did not occur in blood-derived CD3+ T cells. Following an increase in gut-homing integrin α4β7, blood-derived CD3+ T cells carrying PEDV migrated to the intestines via blood circulation and transferred the virus to intestinal epithelial cells through cell-to-cell contact in neonatal piglets. Our findings have significant implications for understanding PEDV pathogenesis in neonatal piglets, which is essential for developing innovative therapies to prevent PEDV infection.
Highlights
Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), an acute and highly contagious enteric viral disease [1,2]
The PEDV-pulsed, blood-derived CD3+ T cells labeled with PKH26 and blood-derived CD3+ T cells labeled with Carboxyfluorescein succinimidyl amino ester (CFSE) mixtures were centrifuged at 200× g for 5 min
PEDV-carrying blood-derived CD3+ T cells labeled with PKH26 were checked and analyzed using flow cytometry
Summary
Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), an acute and highly contagious enteric viral disease [1,2]. Numerous studies have suggested that human immunodeficiency virus type-1(HIV-1) can increase the expression of integrin α4β7, but can incorporate integrin α4β7 in lymphocytes to promote lymphocyte-carrying virus migration to gut-associated lymphoid tissue [17,18,19] It is not clear whether the expression of CCR9 and integrin α4β7 is elevated in CD3+ T cells that carry PEDV. Blood-derived CD3+ T cells carrying PEDV reach the intestines via blood circulation, where they cause intestinal infections through cell-to-cell transmission in neonatal piglets. These results have significant implications for understanding PEDV pathogenesis in neonatal piglets, which is essential for developing innovative therapies to prevent PEDV infection
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