Porcine epidemic diarrhea virus (PEDV), a member of the genera Alphacoronavirus in the family Coronaviridae, causes acute diarrhea/vomiting, dehydration and high mortality in seronegative neonatal piglets. For the last three decades, PEDV infection has resulted in significant economic losses in the European and Asian pig industries, but in 2013-2014 the disease was also reported in the US, Canada and Mexico. The PED epidemic in the US, from April 2013 to the present, has led to the loss of more than 10% of the US pig population. The disappearance and re-emergence of epidemic PED indicates that the virus is able to escape from current vaccination protocols, biosecurity and control systems. Endemic PED is a significant problem, which is exacerbated by the emergence (or potential importation) of multiple PEDV variants. Epidemic PEDV strains spread rapidly and cause a high number of pig deaths. These strains are highly enteropathogenic and acutely infect villous epithelial cells of the entire small and large intestines although the jejunum and ileum are the primary sites. PEDV infections cause acute, severe atrophic enteritis accompanied by viremia that leads to profound diarrhea and vomiting, followed by extensive dehydration, which is the major cause of death in nursing piglets. A comprehensive understanding of the pathogenic characteristics of epidemic or endemic PEDV strains is needed to prevent and control the disease in affected regions and to develop an effective vaccine. This review focuses on the etiology, epidemiology, disease mechanisms and pathogenesis as well as immunoprophylaxis against PEDV infection.

In South Korea, where avian infl uenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine infl uenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/ Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. To determine whether the novel canine infl uenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this infl uenza virus (H3N2) isolate. The beagles shed virus through nasal excretion, seroconverted, and became ill with severe necrotizing tracheobronchitis and bronchioalveolitis with accompanying clinical signs (e.g., high fever). Consistent with histologic observation of lung lesions, large amounts of avian infl uenza virus binding receptor (SAα 2,3-gal) were identifi ed in canine tracheal, bronchial, and bronchiolar epithelial cells, which suggests potential for direct transmission of avian infl uenza virus (H3N2) from poultry to dogs. Our data provide evidence that dogs may play a role in interspecies transmission and spread of infl uenza virus.

Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.

To understand the progression of porcine epidemic diarrhea virus infection, we inoculated gnotobiotic pigs with a newly emerged US strain, PC21A, of the virus. At 24–48 hours postinoculation, the pigs exhibited severe diarrhea and vomiting, fecal shedding, viremia, and severe atrophic enteritis. These findings confirm that strain PC21A is highly enteropathogenic.

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in nursing piglets. Following its first detection in the United States in February 2014, additional PDCoV strains have been identified in the United States and Canada. Currently, no treatments or vaccines for PDCoV are available. In this study, U.S. PDCoV strain OH-FD22 from intestinal contents of a diarrheic pig from Ohio was isolated in swine testicular (ST) and LLC porcine kidney (LLC-PK) cell cultures by using various medium additives. We also isolated PDCoV [OH-FD22(DC44) strain] in LLC-PK cells from intestinal contents of PDCoV OH-FD22 strain-inoculated gnotobiotic (Gn) pigs. Cell culture isolation and propagation were optimized, and the isolates were serially propagated in cell culture for >20 passages. The full-length S and N genes were sequenced to study PDCoV genetic changes after passage in Gn pigs and cell culture (passage 11 [P11] and P20). Genetically, the S and N genes of the PDCoV isolates were relatively stable during the first 20 passages in cell culture, with only 5 nucleotide changes, each corresponding to an amino acid change. The S and N genes of our sequenced strains were genetically closely related to each other and to other U.S. PDCoV strains, with the highest sequence similarity to South Korean strain KNU14-04. This is the first report describing cell culture isolation, serial propagation, and biological and genetic characterization of cell-adapted PDCoV strains. The information presented in this study is important for the development of diagnostic reagents, assays, and potential vaccines against emergent PDCoV strains.