The Emergence of Novel Variants of the Porcine Epidemic Diarrhea Virus Spike Gene from 2011 to 2023
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The porcine epidemic diarrhea virus (PEDV) has caused severe economic losses in the pig industry. Since its discovery, the virus has spread in pig herds for more than 50 years. Many new features have been found in the PEDV spike genes. In this study, 123 representative S genes were used to analyze their characteristics across strains. Phylogenetic analysis revealed that PEDV can be divided into nine groups: G1a, G1b, G1c, G1d, G2a, G2b, G2c, G2d, and G3. In addition, 21 different lengths of the S gene were found. Analysis of the amino acid insertion and deletion sites revealed that most deletions and insertions occurred in the loops of the spike quaternary structure, primarily in the D0 and N‐terminal domains (NTDs). According to the above results, PEDV has undergone considerable evolution, possibly under the immune pressure of vaccination. These results are highly important for understanding the current epidemic situation of PEDV.Vero cell
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Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world's swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan dose-dependently inhibited a PEDV infection at 24 h post-infection (EC 50 value = 0.67 μM). We found that Fan mainly affected the PEDV replication phase but also inhibited PEDV at the attachment and internalization stages of the viral life cycle. Mechanistically, Fan blocked the autophagic flux in PEDV-infected cells by regulating the expression of autophagy-related proteins and changing PEDV virus particles. In summary, Fan inhibits PEDV infection by blocking the autophagic flux in cells. Our findings will help develop new strategies to prevent and treat PEDV infection.
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Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and even death in piglets, resulting in significant economic losses to the pig industry. Because of the ongoing mutation of PEDV, there might be variations between the vaccine strain and the prevailing strain, causing the vaccine to not offer full protection against different PEDV variant strains. Therefore, it is necessary to develop anti-PEDV drugs to compensate for vaccines. This study confirmed the anti-PEDV effect of licorice extract (Le) in vitro and in vivo . Le inhibited PEDV replication in a dose-dependent manner in vitro . By exploring the effect of Le on the life cycle of PEDV, we found that Le inhibited the attachment, internalization, and replication stages of the virus. In vivo , all five piglets in the PEDV-infected group died within 72 h. In comparison, the Le-treated group had a survival rate of 80 % at the same time, with significant relief of clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Our results suggested that Le can exert anti-PEDV effects in vitro and in vivo . Le is effective and inexpensive; therefore it has the potential to be developed as a new anti-PEDV drug.
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Abstract Porcine epidemic diarrhea virus (PEDV) is an etiological agent of porcine epidemic diarrhea (PED), causing dehydration, vomiting, and acute watery diarrhea. Because it has a high mortality rate in neonatal piglets, PEDV is one of the critical pathogens affecting the swine industry. Since PEDV has shown rapid spreading in herds of swine, early diagnosis of this virus is very important to control the disease. Serological diagnosis test is a simple, rapid method for detecting PEDV infected pigs, and the development of PEDV-specific antibodies is essential for an accurate serological diagnostic test. Because conventional methods of development of monoclonal antibodies are time and hand-consuming work, recombinant antibodies are considered as an alternative strategy for the development of target-specific monoclonal antibodies. Peptibody is one of the promising recombinant antibodies that target-specific peptide is fused with the Fc domain of immunoglobulin G. The peptibody which have a specificity of peptides and immune function of Fc region as advantages have developed for therapeutic and diagnostic purpose. Here, we generated a PEDV-specific peptibody (PEDV-PB) that is fused with PEDV-specific peptide and mouse IgG2b Fc region. PEDV-specific peptide sequences were discovered by random phage display library and PEDV-PB was produced from Chinese hamster ovary (CHO) cells. PEDV-PB showed highly specific binding in several serological tests for PEDV, such as western blotting, immunofluorescence assay, and enzyme-linked immunosorbent assay. Our results suggest that PEDV-PB is very useful for the development of a rapid detection kit for PEDV.
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Abstract Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the most abundant trichothecene in food and feed, causes vomit and diarrhea in animals and human. However, whether DON exposure could affect PEDV infection remains unknown. Herein, we investigated the impacts of DON on entry and replication of PEDV, morbidity situation of piglets and the mechanisms involved. In vivo , twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 μg/kg DON, respectively. We observed significant increases in the diarrhea rates, the villous injury of jejunums and the PEDV proliferation of duodenum, jejunum, ileum and mesenterium of piglets in experimental groups compared with control. Additionally, the autophagosome-like vesicles and the autophagy-related protein expressions were also increased in experimental groups. In vitro , we observed that, approximately 2 hrs post-infection, 0.1, 0.5 and 1.0 μM DON promoted PEDV entry ( P < 0.05) in IPEC-J2s and resulted in tight junction protein occludin internalization. Knockdown of occludin and CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of autophagy-induced occludin internalization in DON-promoted PEDV entry. We also observed that, 24 hrs post-infection, a significant increase in PEDV replication after 0.1, 0.5 and 1.0 μM DON treatment, along with the induction of a complete autophagy. Specifically, deletion of LC3B indicated a crucial role of autophagy in DON-promoted PEDV replication. Pretreatment with SB202190, a p38 signaling inhibitor, abolished the induction of autophagy. Furthermore, downregulation of type I interferon revealed that DON contributed PEDV to escape innate immune. Mechanistically, DON-caused innate immune escape was related to the upregulation of LC3B, which further inhibited STING phosphorylation. Taken together, DON could promote PEDV infection by inducing occludin internalization and innate immune escape via triggering p38-mediated autophagy. Author summary Porcine epidemic diarrhea (PED), a devastating enteric disease, leads to catastrophic economic loss to the global pig industry. Its primary pathogen is the coronavirus PED virus (PEDV). Growing evidence indicates that pathogen infection is not the only factor of PED outbreaks, other non-infectious factors is also related to this disease. We guessed some ubiquitous substances, such as deoxynivalenol (DON), that lead to pig intestinal epithelial cell stress might encourage the progress and spread of PED. In the present study, the weaning piglets infected naturally with PEDV and the IPEC-J2 cell line were selected as models to explore the effects of DON on PEDV infection, morbidity and gut barrier. Our results showed that DON exposure can promote PEDV infection in vitro and in vivo , and the underlying mechanism might be related to LC3B-mediated autophagy. Our findings reveal new pathways for developing potential novel antiviral strategies against PEDV infection.
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Porcine epidemic diarrhea virus (PEDV) has caused enormous economic losses to the swine industry worldwide in recent years. Puerarin (PR) has been reported to exert an antiviral effect. This study was conducted with both PEDV-infected Vero cells and neonatal pigs to determine the effect of PR on PEDV infection and to elucidate the underlying mechanisms by a proteomic analysis. Twenty-four piglets fed a milk replacer were randomly allocated into one of three groups (Control, PEDV, and PEDV+PR). After a 5-day period of adaption, piglets (n = 8/group) in the PEDV+PR were orally administered with PR (0.5 mg/kg body weight) between days 5 and 9, whereas piglets in the other two groups received the same volume of liquid milk replacer. On day 9, piglets were orally administered with either sterile saline or PEDV (Yunnan province strain) at 104.5 TCID50 (50% tissue culture infectious dose) per pig. On day 12 of the trial, jugular vein blood and intestinal samples were collected. In addition, Vero cells were assigned randomly into three groups (Control, PEDV, PEDV+PR). Cells in the PEDV and PEDV+PR groups were infected with PEDV at a multiplicity of infection of 0.01, while cells in the control group were treated with the same volume of sterile saline. One hour later, cells in the Control and PEDV groups were cultured in serum-free DMEM, while those in the PEDV+PR group were supplemented with PR solution. After 36 h of culture, cells were harvested. PR attenuated the reductions of cell proliferation in vitro and growth performance in PEDV-infected piglets, and inhibited PEDV replication and the expression of several cytokines (including IL-8) both in vitro and in vivo. Proteomic analyses showed that the abundance of 29 proteins in the ileum was altered by PEDV infection and was restored to the control level by PR. Pathway analyses revealed that PR restored the expression of several interferon-stimulated genes and selectively upregulated the expression of guanylate binding proteins. Western blot analyses showed that PR supplementation inhibited the PEDV-induced NF-κB activation. Collectively, these results indicate PR could exert antiviral and anti-inflammatory effects in piglets infected with PEDV.
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Puerarin
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More recently emerging strains of porcine epidemic diarrhea virus (PEDV) cause severe diarrhea and especially high mortality rates in infected piglets, leading to substantial economic loss to worldwide swine industry. These outbreaks urgently call for updated and effective PEDV vaccines. Better understanding in PEDV biology and improvement in technological platforms for virus production can immensely assist and accelerate PEDV vaccine development. In this study, we explored the ability of PEDV nucleocapsid (N) protein in improving viral yields in cell culture systems. We demonstrated that PEDV N expression positively affected both recovery of PEDV from infectious clones and PEDV propagation in cell culture. Compared to Vero E6 cells, Vero E6 cells expressing PEDV N could accelerate growth of a slow-growing PEDV strain to higher peak titers by 12 hours or enhance the yield of a vaccine candidate strain by two orders of magnitude. Interestingly, PEDV N also slightly enhances replication of porcine reproductive and respiratory virus, a PEDV relative in the Nidovirales order. These results solidify the importance of N in PEDV recovery and propagation and suggest a potentially useful consideration in designing vaccine production platforms for PEDV or closely related pathogens.
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Coronavirus
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Porcine epidemic diarrhea virus (PEDV) has reemerged as the main pathogen of piglets due to its high mutation feature. Monolaurin (ML) is a natural compound with a wide range of antibacterial and antiviral activities. However, the role of ML in PEDV infection is still unknown. This study aimed to evaluate the effect of ML on the growth performance, intestinal function, virus replication and cytokine response in piglets infected with PEDV, and to reveal the mechanism through proteomics analysis. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 days before PEDV infection. Results showed that although there was no significant effect on the growth performance of piglets, ML administration alleviated the diarrhea caused by PEDV infection. ML administration promoted the recovery of intestinal villi, thereby improving intestinal function. Meanwhile, PEDV replication was significantly inhibited, and PEDV-induced expression of IL-6 and IL-8 were decreased with ML administration. Proteomics analyses showed that 38 proteins were differentially expressed between PEDV and ML+PEDV groups and were significantly enriched in the interferon-related pathways. This suggests ML could promote the restoration of homeostasis by regulating the interferon pathway. Overall, the present study demonstrated ML could confer a protective effect against PEDV infection in piglets and may be developed as a drug or feed additive to prevent and control PEDV disease.
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Porcine epidemic diarrhea virus (PEDV), which first emerged in the United States in 2013, spread throughout the U.S. hog population. Limited preemptive knowledge impeded the understanding of PEDV introduction, spread, and prospective economic impacts in the United States. To assess these impacts, this article reviews the timeline of PEDV in the United States and the corresponding impacts. PEDV is a supply-impacting disease and is not demand inhibiting, as pork demand remained strong since PEDV first appeared. Pig losses reached significant levels during September 2013 through August 2014, with the majority of pork production impacts occurring in 2014. PEDV had differing impacts for subsectors of the pork industry. A budget model demonstrates that producers could have had pig losses and decreases in productivity proportionally smaller than price increases, resulting in net returns above what was expected before the major outbreak of PEDV. Previous literature is reviewed to identify the potential main industry beneficiaries of the PEDV outbreaks in the United States. As a result of reduced volumes of available pig and hog supplies, reductions in annual returns likely occurred for packers, processors, distributors, and retailers. In addition, pork consumers who experienced reduced-supply-induced pork-price increases were likely harmed directly by higher prices paid for pork and indirectly as prices of competing meats were also likely strengthened by PEDV. This article also identifies future considerations motivated by the appearance of PEDV in the United States, such as discussions of industry-wide efficiency and competitive advantage, the future role of PEDV vaccines, enhancement in biosecurity measures, and consumer perceptions of food safety and insecurity.
Biosecurity
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Since 2010,porcine epidemic diarrhea in newborn piglets seriously outbroke in most parts of China and caused huge economic losses to the pig industry. For the analysis of epidemic and genetic variation of porcine epidemic diarrhea virus( PEDV) in Zhejiang Province,PEDV in clinical samples collected during 2010-2013 was detected by RT-PCR based on N-terminal of S gene,and fragments of 41 sequences were analyzed for variation of S1gene. The results showed that the PEDV clinical detection rate increased from 42. 86% in 2010 to over 70% in2013. The detection rate was significantly lower in July and August and was more than 50% across Zhejiang province. Sequencing analysis showed that the S gene of clinical detected strains were heterogenous with that of PEDV CV777,indicating that the current epidemic strain probably makes a new genotype and the mutation of PEDV-S1 gene may be the reason for low immune protection of the existing CV777 strain vaccine.
Acute diarrhea
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