Porcine epidemic
diarrhea (PED) is an acute, highly contagious intestinal
swine disease caused by porcine epidemic diarrhea virus (PEDV). In addition to known PEDV
infection targets (villous small intestinal epithelial cells), recent reports suggest that dendritic cells (DCs) may also be targeted by PEDV in vivo. Thus, in this study we used bone marrow-derived dendritic cells (BM-DCs) as an in vitro model of antigen-presenting cells (APCs). Our results revealed that PEDV replicated in BM-DCs and that PEDV
infection of cells inhibited expression of
swine leukocyte antigen II DR (SLA-DR), a key MHC-II molecule involved in antigen presentation and initiation of CD4+ T cell activation. Notably, SLA-DR inhibition in BM-DCs did not require PEDV replication, suggesting that PEDV structural
proteins participated in SLA-DR transcriptional inhibition. Moreover, reporter assay-based screening indicated that PEDV envelope
protein blocked activation of SLA-DRα and β promoters, as did PEDV-ORF3
protein when present during PEDV replication. Meanwhile, treatment of PEDV-infected BM-DCs with
MG132, a
ubiquitin-
proteasome degradation pathway inhibitor, did not restore SLA-DR
protein levels. Additionally, PEDV
infection of BM-DCs did not alter SLA-DR ubiquitination status, suggesting that PEDV
infection did not affect SLA-DR degradation. Furthermore, additions of PEDV structural
proteins to HEK-293T-SLA-DR stably transfected cells had no effect on SLA-DR
protein levels, indicating that PEDV-mediated inhibition of SLA-DR expression acted mainly at the transcriptional level, not at the
protein level. These results provide novel insights into PEDV pathogenic mechanisms and viral-host interactions.