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Frontiers in Veterinary Science 2023Porcine deltacoronavirus (PDCoV) is a newly emerging and important porcine enteropathogenic coronavirus that seriously threatens the swine industry in China and...
Porcine deltacoronavirus (PDCoV) is a newly emerging and important porcine enteropathogenic coronavirus that seriously threatens the swine industry in China and worldwide. We conducted a systematic review and meta-analysis to access the prevalence of PDCoV infection in pig population from mainland China. Electronic databases were reviewed for PDCoV infection in pig population, and meta-analysis was performed to calculate the overall estimated prevalence using random-effect models. Thirty-nine studies were included (including data from 31,015 pigs). The overall estimated prevalence of PDCoV infection in pigs in China was 12.2% [95% confidence interval (CI), 10.2-14.2%], and that in Central China was 24.5% (95%CI, 16.1-32.9%), which was higher than those in other regions. During 2014-2021, the estimated prevalence of PDCoV infection was the highest in 2015 at 20.5% (95%CI, 10.1-31.0%) and the lowest in 2021 at 4.8% (95%CI, 2.3-7.3%). The prevalence of PDCoV infection in sows was 23.6% (95%CI, 15.8-31.4%), which was higher than those in suckling piglets, nursery piglets, and finishing pigs. The prevalence of PDCoV infection was significantly associated with sampling region, sampling year, pig stage, and clinical signs (diarrhea). This study systematically evaluated the epidemiology of PDCoV infection in Chinese pig population. The findings provide us with a comprehensive understanding of PDCoV infection and are beneficial for establishing new controlling strategies worldwide.
PubMed: 37483295
DOI: 10.3389/fvets.2023.1198593 -
Journal of Virology Jun 2024Porcine deltacoronavirus (PDCoV) is an enteric pathogenic coronavirus that causes acute and severe watery diarrhea in piglets and has the ability of cross-species...
Porcine deltacoronavirus (PDCoV) is an enteric pathogenic coronavirus that causes acute and severe watery diarrhea in piglets and has the ability of cross-species transmission, posing a great threat to swine production and public health. The interferon (IFN)-mediated signal transduction represents an important component of virus-host interactions and plays an essential role in regulating viral infection. Previous studies have suggested that multifunctional viral proteins encoded by coronaviruses antagonize the production of IFN via various means. However, the function of these viral proteins in regulating IFN-mediated signaling pathways is largely unknown. In this study, we demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I IFN-mediated JAK-STAT signaling pathway. We identified that PDCoV infection stimulated but delayed the production of IFN-stimulated genes (ISGs). In addition, PDCoV inhibited JAK-STAT signal transduction by targeting the nuclear translocation of STAT1 and ISGF3 formation. Further evidence showed that PDCoV N is the essential protein involved in the inhibition of type I IFN signaling by targeting STAT1 nuclear translocation via its C-terminal domain. Mechanistically, PDCoV N targets STAT1 by interacting with it and subsequently inhibiting its nuclear translocation. Furthermore, PDCoV N inhibits STAT1 nuclear translocation by specifically targeting KPNA2 degradation through the lysosomal pathway, thereby inhibiting the activation of downstream sensors in the JAK-STAT signaling pathway. Taken together, our results reveal a novel mechanism by which PDCoV N interferes with the host antiviral response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that receives increased attention and seriously threatens the pig industry and public health. Understanding the underlying mechanism of PDCoV evading the host defense during infection is essential for developing targeted drugs and effective vaccines against PDCoV. This study demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I interferon signaling by targeting STAT1, which is a crucial signal sensor in the JAK-STAT signaling pathway. Further experiments suggested that PDCoV N-mediated inhibition of the STAT1 nuclear translocation involves the degradation of KPNA2, and the lysosome plays a role in KPNA2 degradation. This study provides new insights into the regulation of PDCoV N in the JAK-STAT signaling pathway and reveals a novel mechanism by which PDCoV evades the host antiviral response. The novel findings may guide us to discover new therapeutic targets and develop live attenuated vaccines for PDCoV infection.
PubMed: 38829137
DOI: 10.1128/jvi.00334-24 -
MSystems Mar 2024Porcine deltacoronavirus (PDCoV) is an enteropathogenic coronavirus that mainly causes diarrhea in suckling piglets, and also has the potential for cross-species...
Porcine deltacoronavirus (PDCoV) is an enteropathogenic coronavirus that mainly causes diarrhea in suckling piglets, and also has the potential for cross-species transmission. However, there are still no commercial vaccines available to prevent and control PDCoV infection. In this study, PDCoV strain HNZK-02 was serially propagated for up to 150 passages and the amino acid changes have mainly occurred in the S protein during serial passage which caused structure change. PDCoV HNZK-02-passage 5 (P5)-infected piglets exhibited acute and severe watery diarrhea, an obvious intestinal damage, while the piglets infected with PDCoV HNZK-02-P150 showed no obvious clinical signs, weak intestinal lesions, and lower viral loads in rectal swabs and various tissues. Compared with the PDCoV HNZK-02-P5 infection, HNZK-02-P150 infection resulted in a decrease in intestinal mucosal permeability and pro-inflammatory cytokines. Moreover, PDCoV HNZK-02-P5 infection had significantly reduced bacterial diversity and increased relative abundance of opportunistic pathogens, while PDCoV HNZK-02-P150 infection did not significantly affect the bacterial diversity, and the relative abundance of probiotics increased. Furthermore, the alterations of gut microbiota were closely related to the change of pro-inflammatory factor. Metagenomics prediction analysis demonstrated that HNZK-02-P150 modulated the tyrosine metabolism, Nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway, and lipopolysaccharide biosynthesis, which coincided with lower inflammatory response and intestinal permeability in the piglets infected with HNZK-02-P150. In conclusion, the PDCoV HNZK-02 was successfully attenuated by serial passage , and the changes of S gene, metabolic function, and gut microbiota may contribute to the attenuation. The PDCoV HNZK-02-P150 may have the potential for developing live-attenuated vaccine.IMPORTANCEPorcine deltacoronavirus (PDCoV) is an enteropathogen causing severe diarrhea, dehydration, and death in nursing piglets, devastating great economic losses for the global swine industry, and has cross-species transmission and zoonotic potential. There are currently no approved treatments or vaccines available for PDCoV. In addition, gut microbiota has an important relationship with the development of many diseases. Here, the PDCoV virulent HNZK-02 strain was successfully attenuated by serial passage on cell cultures, and the pathogenesis and effects on the gut microbiota composition and metabolic function of the PDCoV HNZK-02-P5 and P150 strains were investigated in piglets. We also found the genetic changes in the S protein during passage and the gut microbiota may contribute to the pathogenesis of PDCoV, while their interaction molecular mechanism would need to be explored further.
Topics: Animals; Swine; Virulence; Gastrointestinal Microbiome; Serial Passage; Swine Diseases; Cell Culture Techniques; Diarrhea; Vaccines; Homeostasis
PubMed: 38349151
DOI: 10.1128/msystems.01346-23 -
Microbiology Spectrum Dec 2023Porcine deltacoronavirus (PDCoV) is a newly emerged enteric virus threatening pig industries worldwide. Our previous work showed that PDCoV enters porcine kidney (PK-15)...
Porcine deltacoronavirus (PDCoV) is a newly emerged enteric virus threatening pig industries worldwide. Our previous work showed that PDCoV enters porcine kidney (PK-15) cells through a caveolae-dependent pathway, but the entry mechanism for PDCoV into swine testicle (ST) cells remains unclear. Mechanisms of virus entry can be different with different virus isolates and cell types. Here, we determined that PDCoV enters ST cells via clathrin-mediated endocytosis. Additionally, we found that PDCoV entry does not require Rab5, Rab7, or Rab11. These findings provide additional understanding of the entry mechanisms of PDCoV and possible antiviral targets.
Topics: Animals; Swine; Endocytosis; Deltacoronavirus; Virus Internalization; Clathrin; Swine Diseases; Coronavirus Infections
PubMed: 37962380
DOI: 10.1128/spectrum.02553-23 -
Porcine Deltacoronavirus Occurrence in the United States Breeding Herds since Its Emergence in 2014.Viruses Mar 2024PDCoV, an enveloped RNA virus, causes atrophic enteritis in neonatal piglets, leading to diarrhea, malabsorption, dehydration, and death. The study aims to fill the gap...
PDCoV, an enveloped RNA virus, causes atrophic enteritis in neonatal piglets, leading to diarrhea, malabsorption, dehydration, and death. The study aims to fill the gap in the current epidemiological information about PDCoV in the U.S. pig population after its emergence in 2014. Data from the Morrison Swine Health Monitoring Project (MSHMP) between January 2015 and December 2023 were analyzed, representing approximately 60% of the U.S. breeding herd. Participating herds report weekly PDCoV health status. In total, 244 PDCoV outbreaks occurred in 186 sites from 22 production systems across 16 states. Case counts peaked during winter, and incidence ranged from 0.44% in 2017 to 4.28% in 2023. For sites that experienced more than one PDCoV outbreak during the study period, the interval between outbreaks was a median of 2.11 years. The South and Midwest regions reported the majority of cases. In 2017, a shift in the spatial distribution of cases from the Midwest to the South was observed. The findings underscore the importance of continued monitoring and strengthened control measures to mitigate the impact of PDCoV in U.S. breeding herds.
Topics: Animals; United States; Swine; Coronavirus; Coronavirus Infections; Deltacoronavirus; Swine Diseases
PubMed: 38543810
DOI: 10.3390/v16030445 -
Nature Communications Jul 2023
PubMed: 37474576
DOI: 10.1038/s41467-023-40128-w -
Frontiers in Veterinary Science 2024Porcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea,...
INTRODUCTION
Porcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. However, the underlying pathogenic mechanisms of PDCoV infection and the effects of PDCoV infection on host transcripts and metabolites remain incompletely understood.
METHODS
This study investigated a combined transcriptomic and metabolomic analysis of porcine intestinal epithelial cells (IPEC-J2) following PDCoV infection by LC/MS and RNA-seq techniques. A total of 1,401 differentially expressed genes and 254 differentially accumulated metabolites were detected in the comparison group of PDCoV-infected vs. mock-infected.
RESULTS AND DISCUSSION
We found that PDCoV infection regulates gene sets associated with multiple signaling pathways, including the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, MAPK signaling pathway, chemokine signaling pathway, ras signaling pathway and so on. Besides, the metabolomic results showed that biosynthesis of cofactors, nucleotide metabolism, protein digestion and absorption, and biosynthesis of amino acid were involved in PDCoV infection. Moreover, integrated transcriptomics and metabolomics analyses revealed the involvement of ferroptosis in PDCoV infection, and exogenous addition of the ferroptosis activator erastin significantly inhibited PDCoV replication. Overall, these unique transcriptional and metabolic reprogramming features may provide a better understanding of PDCoV-infected IPEC-J2 cells and potential targets for antiviral treatment.
PubMed: 38855411
DOI: 10.3389/fvets.2024.1359547 -
Current Issues in Molecular Biology Jun 2024In the SARS-CoV-2 lineage, RNA elements essential for its viral life cycle, including genome replication and gene expression, have been identified. Still, the precise...
In the SARS-CoV-2 lineage, RNA elements essential for its viral life cycle, including genome replication and gene expression, have been identified. Still, the precise structures and functions of these RNA regions in coronaviruses remain poorly understood. This lack of knowledge points out the need for further research to better understand these crucial aspects of viral biology and, in time, prepare for future outbreaks. In this research, the in silico analysis of the RNA structures that act in the alpha-, beta-, gamma-, and deltacoronavirus genera has provided a detailed view of the presence and adaptation of the structures of these elements in coronaviruses. The results emphasize the importance of these elements in viral biology and their variability between different viral variants. Some coronavirus variants in some groups, depending on the element (stem-loop1 and -2; pseudoknot stem-loop1 and -2, and s2m), exhibited functional adaptation. Additionally, the conformation flexibility of the s2m element in the SARS variants was determined, suggesting a coevolution of this element in this viral group. The variability in secondary structures suggests genomic adaptations that may be related to replication processes, genetic regulation, as well as the specific pathogenicity of each variant. The results suggest that RNA structures in coronaviruses can adapt and evolve toward different viral variants, which has important implications for viral adaptation, pathogenicity, and future therapeutic strategies.
PubMed: 38921015
DOI: 10.3390/cimb46060344 -
Viruses Apr 2024Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts...
Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) by analyzing the transcriptome at different time points post-infection (12 h, 24 h, 48 h). Differential gene analysis revealed a total of 3560, 5193, and 4147 differentially expressed genes (DEGs) at 12 h, 24 h, and 48 h, respectively. The common genes among the DEGs at all three time points were enriched in biological processes related to cytokine production, extracellular matrix, and cytokine activity. KEGG pathway analysis showed enrichment of genes involved in the p53 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. Further analysis of highly expressed genes among the DEGs identified significant changes in the expression levels of BUB1, DDIT4, ATF3, GBP2, and IRF1. Comparison of transcriptome data at 24 h with other time points revealed 298 DEGs out of a total of 6276 genes. KEGG analysis of these DEGs showed significant enrichment of pathways related to viral infection, specifically the PI3K-Akt and P38 MAPK pathways. Furthermore, the genes EFNA1 and KITLG, which are associated with viral infection, were found in both enriched pathways, suggesting their potential as therapeutic or preventive targets for PDCoV infection. The enhancement of PDCoV infection in HIEC-6 was observed upon inhibition of the PI3K-Akt and P38 MAPK signaling pathways using sophoridine. Overall, these findings contribute to our understanding of the molecular mechanisms underlying PDCoV infection in HIEC-6 cells and provide insights for developing preventive and therapeutic strategies against PDCoV infection.
Topics: Animals; Humans; Cell Line; Coronavirus Infections; Deltacoronavirus; Gene Expression Profiling; Host-Pathogen Interactions; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Swine; Swine Diseases; Transcriptome
PubMed: 38675921
DOI: 10.3390/v16040579 -
BMC Veterinary Research Jan 2024Porcine deltacoronavirus (PDCoV) is one of the emerging swine enteric coronaviruses (SECoVs), which has been widely prevalent in the North America and Asia. In addition...
BACKGROUND
Porcine deltacoronavirus (PDCoV) is one of the emerging swine enteric coronaviruses (SECoVs), which has been widely prevalent in the North America and Asia. In addition to causing severe diarrhea in piglets, PDCoV also shows the potential to infect diverse host species, including calves, chickens, turkey poults, and humans. However, the clinical pathogenicity and genetic evolution of PDCoV is still not fully understood.
RESULTS
Here, we recorded an outbreak of a novel recombinant PDCoV strain (CHN-HeN06-2022) in a large nursery fattening pig farm. Genomic analysis showed that the CHN-HeN06-2022 strain shared 98.3-98.7% sequence identities with the Chinese and American reference strains. To clarify the evolutionary relationships, phylogenetic analysis was performed using the PDCoV genome sequences available in the GenBank database. Based on genetic distance and geographical distribution, the phylogenetic tree clearly showed that all the PDCoV sequences could be divided into lineage 1 and lineage 2, which were further classified into sublineage 1.1 (Chinese strains), 1.2 (the North American strains), 2.1 (the Southeast Asian strains), and 2.2 (Chinese strains). Corresponding to the evolutionary tree, we found that, compared to lineage 1, lineage 2 strains usually contain a continuous 6-nt deletion in Nsp2 and a 9-nt deletion in Nsp3, respectively. Furthermore, recombination analysis suggested that the CHN-HeN06-2022 occurred segments exchange crossed Nsp2 and Nsp3 region between sublineage 1.1 and sublineage 2.1. Combined with previously reported recombinant strains, the highest recombination frequency occurred in Nsp2, Nsp3, and S gene. Additionally, we identified a total of 14 amino acid sites under positive selection in spike protein, most of which are located in the regions related with the viral attachment, receptor binding, and membrane fusion.
CONCLUSIONS
Taken together, our studies provide novel insights into the genetic diversity and adaptive evolution of PDCoV. It would be helpful to the development of vaccine and potential antiviral agent.
Topics: Humans; Animals; Cattle; Swine; Chickens; Phylogeny; Turkeys; Genetic Variation; Deltacoronavirus
PubMed: 38200538
DOI: 10.1186/s12917-023-03863-2