Porcine epidemic diarrhea virus infection: Pathogenesis, epidemiology, pathogenesis and prevention

Abstract

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus in the family Coronaviridae. It causes acute diarrhea/vomiting, dehydration, and high mortality in seronegative newborn piglets. Over the past three decades, PEDV infection has caused significant economic losses to the swine industry in Europe and Asia, but in 2013-2014, the disease was also reported in the United States, Canada, and Mexico. Since April 2013, PED outbreaks in the United States have resulted in a loss of more than 10% of the U.S. swine population.

The disappearance and re-emergence of epidemic PED indicates that the virus can evade current vaccination programs, biosecurity, and control systems. Endemic PED is a significant problem, exacerbated by the emergence (or potential importation) of multiple PEDV variants. Epidemic PEDV strains spread rapidly, leading to mass mortality in pigs. These strains are highly enteric pathogenic, acutely infecting the villous epithelial cells of the entire small and large intestines, but the jejunum and ileum are the primary sites of infection. Porcine epidemic diarrhea virus (PEDV) infection causes acute, severe atrophic enteritis accompanied by viremia, leading to severe diarrhea and vomiting, followed by severe dehydration, a leading cause of death in suckling piglets. A comprehensive understanding of the pathogenic characteristics of epidemic or endemic PEDV strains is needed to prevent and control the disease in affected areas and to develop effective vaccines. This review focuses on the etiology, epidemiology, disease mechanisms, pathogenesis, and immunoprophylaxis of PEDV infection.

Introduction

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae in the order Nidovirales. It causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, resulting in significant economic losses. The disease was initially reported in the swine industry in Europe and Asia over the past 30 years, with the virus first appearing in England and Belgium in the early 1970s. More recently, PEDV has also been reported in the United States. Since then, the virus has spread rapidly throughout the United States and to other North American countries, including Canada and Mexico. Due to the significant impact of PEDV, the US swine industry lost nearly 10% of its domestic hog population, equivalent to approximately 7 million piglets, after just one year of epidemic.

The similar epidemiological and clinical characteristics of PEDV and another type of alpha coronavirus, transmissible gastroenteritis virus (TGEV), complicate diagnosis and require differential laboratory testing. Since the emergence of a naturally occurring spike protein deletion mutant of TGEV—porcine respiratory coronavirus (PRCV)—in 1984, TGEV transmission has decreased in PRCV-seropositive pig herds due to cross-protective immunity with TGEV. In contrast, PEDV continues to spread globally and cause economic problems.

Based on genetic analysis, the Coronaviridae family can be divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Bats are considered the genetically derived hosts of Alpha and Beta coronaviruses, while birds are considered suspected hosts of Gamma and Delta coronaviruses. In different regions of the United States where PEDV is prevalent, a genetically distinct novel coronavirus—porcine d-coronavirus (PDCoV)—frequently co-occurs in diarrheal fecal samples from pigs. PDCoV has been reported to have lower clinical impact and disease severity in the field than PEDV. A recent study confirmed that PDCoV is enteropathogenic in pigs, acutely infecting the small intestine and causing severe diarrhea and/or vomiting, as well as atrophic enteritis, with clinical symptoms similar to PEDV and TGEV infections. Currently, differential diagnosis of PEDV, PDCoV, and TGEV is crucial for controlling viral epidemic diarrhea in US swine farms.

This review focuses on the current understanding of the etiology, epidemiology, disease mechanisms, and pathogenesis of PEDV, as well as control measures that can be used to prevent PEDV infection.

Conclusion

The disappearance and re-emergence of endemic PEDV demonstrates that PEDV can effectively evade current vaccination programs, biosecurity, and control systems. Endemic PEDV is a significant problem, exacerbated by the emergence of multiple PEDV variants or their potential introduction into other countries. Endemic PEDV strains spread rapidly, causing significant pig mortality and economic losses. These strains are highly enteropathogenic, acutely infecting the villous epithelial cells of the entire small and large intestines, although the jejunum and ileum are the primary sites of infection. PEDV infection causes acute, severe atrophic enteritis with viremia (viral RNA), leading to severe diarrhea and vomiting, followed by severe dehydration and electrolyte imbalance, the leading cause of death in suckling piglets. A better understanding of the pathogenic characteristics of endemic or endemic PEDV strains is needed to prevent and control the disease in affected areas and to develop effective vaccines.

The high mortality rate in seronegative suckling piglets infected with PEDV is most likely related to severe dehydration caused by severe villous atrophy. In infected suckling piglets, there is increased proliferation of intestinal crypt cells, an increased number of LGR5+ crypt stem cells, remodeling of damaged intestinal epithelium, and migration of mature intestinal cells to the villus tips. However, these may not be sufficient to prevent severe dehydration in suckling piglets. The time to dehydration in field-plagued PEDV-infected suckling piglets appears too short for animals to recover from the disease through natural epithelial cell renewal via crypt stem cells. Further research is needed to determine the extent to which intestinal stem cells in suckling piglets and weaned piglets organize and migrate to replace PEDV-infected villus epithelial cells. Pharmacological or biological mediators that promote stem cell regeneration or maturation, such as epidermal growth factor, would be interesting targets for attempting to shorten epithelial cell renewal time and reduce PEDV-induced dehydration and death losses.