The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1*0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIV NW9 ; NSDTVGWSW) or Ebola virus (Ebola AY9 ; ATAAATEAY) were determined in this study. The overall peptide-SLA-1*0401 structures resemble, as expected, the general conformations of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of SLA-1*0401 is that Arg 156 has a "one-ballot veto" function in peptide binding, due to its flexible side chain. S-OIV NW9 and Ebola AY9 bind SLA-1*0401 with similar conformations but employ different water molecules to stabilize their binding. The side chain of P7 residues in both peptides is exposed, indicating that the epitopes are "featured" peptides presented by this SLA. Further analyses showed that SLA-1*0401 and human leukocyte antigen (HLA) class I HLA-A*0101 can present the same peptides, but in different conformations, demonstrating cross-species epitope presentation. CTL epitope peptides derived from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding method. Three peptides were identified as potential cross-species influenza virus (IV) CTL epitopes. The binding motif of SLA-1*0401 was proposed, and thermostabilities of key peptide-SLA-1*0401 complexes were analyzed by circular dichroism spectra. Our results not only provide the structural basis of peptide presentation by SLA I but also identify some IV CTL epitope peptides. These results will benefit both vaccine development and swine organ-based xenotransplantation.

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Porcine epidemic diarrhea virus (PEDV) is responsible for the acute infectious swine disease porcine epidemic diarrhea (PED). PED causes damage to the intestine, including villus atrophy and shedding, leading to serious economic losses to the pig industry worldwide. We carried out an in vitro study to investigate cell apoptosis and the cell cycle in a PEDV-infected host using transcriptomic shotgun sequencing (RNA-Seq) to study gene responses to PEDV infection. Results revealed that the PEDV infection reduced proliferation activity, blocked the cell cycle at S-phase and induced apoptosis in IPEC-J2 cells. The expression of gene levels related to ribosome proteins and oxidative phosphorylation were significantly up-regulated post-PEDV infection. Although the significantly down-regulated on PI3K/Akt signaling pathway post-PEDV infection, the regulator-related genes of mTOR signaling pathway exerted significantly up-regulated or down-regulated in IPEC-J2 cells. These results indicated that ribosome proteins and oxidative phosphorylation process were widely involved in the pathological changes and regulation of host cells caused by PEDV infection, and PI3K/AKT and mTOR signaling pathways played a vital role in antiviral regulation in IPEC-J2 cells. These data might provide new insights into the specific pathogenesis of PEDV infection and pave the way for the development of effective therapeutic strategies.

In contrast to colostral immunoglobulins, changes in metabolite composition of ingested colostrum in the gut have received little attention. Here, we characterized the metabolite profiles of colostrum and milk, ingested colostrum and milk, and serum of neonatal calves by liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry metabolomics approaches. Colostrum and milk underwent similar changes in metabolite profiles in the gut after being ingested. These changes were characterized by increases in methionine, glutamate, thymine, and phosphorylcholine. After ingestion, colostrum concentrations of several metabolites, such as γ-aminobutyric acid, glutamate, cinnamic acid, and thymine increased, whereas concentrations of d-ribose, and arginine decreased. These increases and decreases occurred in a time-dependent manner and were associated with alanine, aspartate, glutamate, and pyrimidine metabolism, and valine, leucine, and isoleucine biosynthesis, respectively. Meanwhile, similar changes in serum metabolites were also observed in neonatal calves fed colostrum, which implies that colostrum metabolites are transported across the small intestine and into the bloodstream. In addition, several metabolites of ingested milk were detected in the gut, and were also transferred to the bloodstream. These metabolites were related to phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine biosynthesis, the citrate cycle, and histidine metabolism. These findings reveal that the serum metabolome of neonatal calves' changes as a result of ingesting colostrum, which can provide health-related benefits in early life.