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Viruses Jun 2019Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus with worldwide distribution. PDCoV belongs to the (DCoV) genus, which mainly includes...
Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus with worldwide distribution. PDCoV belongs to the (DCoV) genus, which mainly includes avian coronaviruses (CoVs). PDCoV has the potential to infect human and chicken cells in vitro, and also has limited infectivity in calves. However, the origin of PDCoV in pigs, the host range, and cross-species infection of PDCoV still remain unclear. To determine whether PDCoV really has the ability to infect chickens in vivo, the three lines of chicken embryos and specific pathogen free (SPF) chickens were inoculated with PDCoV HNZK-02 strain to investigate PDCoV infection in the current study. Our results indicated that PDCoV can infect chicken embryos and could be continuously passaged on them. Furthermore, we observed that PDCoV-inoculated chickens showed mild diarrhea symptoms and low fecal viral RNA shedding. PDCoV RNA could also be detected in multiple organs (lung, kidney, jejunum, cecum, and rectum) and intestinal contents of PDCoV-inoculated chickens until 17 day post-inoculation by real-time quantitative PCR (qRT-PCR). A histology analysis indicated that PDCoV caused mild lesions in the lung, kidney, and intestinal tissues. These results prove the susceptibility of chickens to PDCoV infection, which might provide more insight about the cross-species transmission of PDCoV.
Topics: Animal Structures; Animals; Cattle; Chick Embryo; Coronavirus; Coronavirus Infections; Diarrhea; Disease Susceptibility; Disease Transmission, Infectious; Feces; Poultry Diseases; Virus Shedding
PubMed: 31234434
DOI: 10.3390/v11060573 -
Microbiology Spectrum Aug 2023
Emergence of a Novel Genotype of Pigeon Deltacoronavirus Closely Related to Porcine Deltacoronavirus HKU15 and Sparrow Deltacoronavirus HKU17 in a Live Poultry Market in Shandong Province, China.
Topics: Swine; Animals; Deltacoronavirus; Columbidae; Sparrows; Poultry; Coronavirus Infections; China; Genotype; Swine Diseases; Phylogeny
PubMed: 37382540
DOI: 10.1128/spectrum.00556-23 -
Journal of Virology Apr 2022Major histocompatibility complex class I (MHC-I) and MHC-II molecules, mainly being responsible for the processing and presentation of intracellular or extracellular...
Major histocompatibility complex class I (MHC-I) and MHC-II molecules, mainly being responsible for the processing and presentation of intracellular or extracellular antigen, respectively, are critical for antiviral immunity. Here, we reported that porcine deltacoronavirus (PDCoV) with the zoonotic potential and potential spillover from pigs to humans, upregulated the expressions of porcine MHC-I (swine leukocyte antigen class I, SLA-I) molecules and SLA-I antigen presentation associated genes instead of porcine MHC-II (SLA-II) molecules both in primary porcine enteroids and swine testicular (ST) cells at the late stage of infection, and this finding was verified . Moreover, the induction of SLA-I molecules by PDCoV infection was mediated through enhancing the expression of NOD-like receptor (NLR) family caspase recruitment domain-containing 5 (NLRC5). Mechanistic studies demonstrated that PDCoV infection robustly elevated retinoic acid-inducible gene I (RIG-I) expression, and further initiated the downstream type I interferon beta (IFN-β) production, which led to the upregulation of NLRC5 and SLA-I genes. Likewise, interferon regulatory factor 1 (IRF1) elicited by PDCoV infection directly activated the promoter activity of NLRC5, resulting in an increased expression of NLRC5 and SLA-I upregulation. Taken together, our findings advance our understanding of how PDCoV manipulates MHC molecules, and knowledge that could help inform the development of therapies and vaccines against PDCoV. MHC-I molecules play a crucial role in antiviral immunity by presenting intracellular antigens to CD8T lymphocytes and eliminating virus-infected cells by natural killer cells' "missing-self recognition." However, the manipulation of MHC molecules by coronaviruses remains poorly understood. Here, we demonstrated that PDCoV, a zoonotic potential coronavirus efficiently infecting cells from broad species, greatly increased the expressions of porcine MHC-I (SLA-I) molecules and MHC-I antigen presentation associated genes but not porcine MHC-II (SLA-II) molecules both and . Mechanistically, the upregulation of MHC-I molecules by PDCoV infection required the master transactivator of MHC-I, NLRC5, which was mediated not only by RIG-I-initiated type I IFN signaling pathway but also by IRF1 induced by PDCoV as it could activate NLRC5 promoter activity. These results provide significant insights into the modification of the MHC class I pathway and may provide a potential therapeutic intervention for PDCoV.
Topics: Animals; Coronavirus Infections; Deltacoronavirus; Gene Expression Regulation; Histocompatibility Antigens Class I; Interferon Regulatory Factor-1; Swine
PubMed: 35311551
DOI: 10.1128/jvi.00158-22 -
Frontiers in Microbiology 2024Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic...
Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic analysis of bird samples from Qinghai Lake, China in 2021 reported the presence of Deltacoronavirus. A specific gene fragment of Deltacoronavirus was detected in fecal samples from wild birds at a positive rate of 5.94% (6/101). Next-generation sequencing (NGS) identified a novel Deltacoronavirus strain, which was closely related to isolates from the United Arab Emirates (2018), China (2022), and Poland (2023). Subsequently the strain was named A/black-headed gull/Qinghai/2021(BHG-QH-2021) upon confirmation of the Cytochrome b gene of black-headed gull in the sample. All available genome sequences of avian Deltacoronavirus, including the newly identified BHG-QH-2021 and 5 representative strains of porcine Deltacoronavirus (PDCoV), were classified according to ICTV criteria. In contrast to , which infects both mammals and birds and shows the possibility of cross-species transmission from bird to mammal host, our analysis revealed that BHG-QH-2021 is classified as . has been reported to infect 5 species of birds but not mammals, suggesting that cross-species transmission of is more prevalent among birds. Recombination analysis traced BHG-QH-2021 origin to dut148cor1 and MW01_1o strains, with MW01_1o contributing the S gene. Surprisingly, SwissModle prediction showed that the optimal template for receptor-binding domain (RBD) of BHG-QH-2021 is derived from the human coronavirus 229E, a member of the Alphacoronavirus, rather than the anticipated RBD structure of PDCoV of Deltacoronavirus. Further molecular docking analysis revealed that substituting the loop 1-2 segments of HCoV-229E significantly enhanced the binding capability of BHG-QH-2021 with human Aminopeptidase N (hAPN), surpassing its native receptor-binding domain (RBD). Most importantly, this finding was further confirmed by co-immunoprecipitation experiment that loop 1-2 segments of HCoV-229E enable BHG-QH-2021 RBD binding to hAPN, indicating that the loop 1-2 segment of the RBD in is a probable key determinant for the virus ability to spill over into humans. Our results summarize the phylogenetic relationships among known Deltacoronavirus, reveal an independent putative avian Deltacoronavirus species with inter-continental and inter-species transmission potential, and underscore the importance of continuous surveillance of wildlife Deltacoronavirus.
PubMed: 38933020
DOI: 10.3389/fmicb.2024.1423367 -
Virus Research Feb 2024Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in...
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The aim of this study was to investigate the anti-PDCoV effects and mechanisms of CEP in LLC-PK1 cells. The results showed that the antiviral activity of CEP was based on direct action on cells, preventing the virus from attaching to host cells and virus replication. Importantly, Surface Plasmon Resonance (SPR) results showed that CEP has a moderate affinity to PDCoV receptor, porcine aminopeptidase N (pAPN) protein. AutoDock predicted that CEP can form hydrogen bonds with amino acid residues (R740, N783, and R790) in the binding regions of PDCoV and pAPN. In addition, RT-PCR results showed that CEP treatment could significantly reduce the transcription of ZBP1, cytokine (IL-1β and IFN-α) and chemokine genes (CCL-2, CCL-4, CCL-5, CXCL-2, CXCL-8, and CXCL-10) induced by PDCoV. Western blot analysis revealed that CEP could inhibit viral replication by inducing autophagy. In conclusion, our results suggest that the anti-PDCoV activity of CEP is not only relies on competing the virus binding with pAPN, but also affects the proliferation of the virus in vitro by downregulating the excessive immune response caused by the virus and inducing autophagy. CEP emerges as a promising candidate for potential anti-PDCoV therapeutic development.
Topics: Animals; Swine; Swine Diseases; Coronavirus; Coronavirus Infections; CD13 Antigens; Deltacoronavirus; Benzylisoquinolines; Benzodioxoles
PubMed: 38145807
DOI: 10.1016/j.virusres.2023.199303 -
Translational Animal Science Apr 2020Postweaning mortality is extremely complex with a multitude of noninfectious and infectious contributing factors. In the current review, our objective is to describe the... (Review)
Review
Postweaning mortality is extremely complex with a multitude of noninfectious and infectious contributing factors. In the current review, our objective is to describe the current state of knowledge regarding infectious causes of postweaning mortality, focusing on estimates of frequency and magnitude of effect where available. While infectious mortality is often categorized by physiologic body system affected, we believe the complex multifactorial nature is better understood by an alternative stratification dependent on intervention type. This category method subjectively combines disease pathogenesis knowledge, epidemiology, and economic consequences. These intervention categories included depopulation of affected cohorts of animals, elimination protocols using knowledge of immunity and epidemiology, or less aggressive interventions. The most aggressive approach to control infectious etiologies is through herd depopulation and repopulation. Historically, these protocols were successful for and swine dysentery among others. Additionally, this aggressive measure likely would be used to minimize disease spread if either a foreign animal disease was introduced or pseudorabies virus was reintroduced into domestic swine populations. Elimination practices have been successful for , porcine reproductive and respiratory syndrome virus, coronaviruses, including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus, swine influenza virus, nondysentery spp., and others. Porcine circovirus type 2 can have a significant impact on morbidity and mortality; however, it is often adequately controlled through immunization. Many other infectious etiologies present in swine production have not elicited these aggressive control measures. This may be because less aggressive control measures, such as vaccination, management, and therapeutics, are effective, their impact on mortality or productivity is not great enough to warrant, or there is inadequate understanding to employ control procedures efficaciously and efficiently. Since there are many infectious agents and noninfectious contributors, emphasis should continue to be placed on those infectious agents with the greatest impact to minimize postweaning mortality.
PubMed: 32705048
DOI: 10.1093/tas/txaa052 -
BioMed Research International 2021This article is aimed at analyzing the structure and function of the spike (S) proteins of porcine enteric coronaviruses, including transmissible gastroenteritis virus...
This article is aimed at analyzing the structure and function of the spike (S) proteins of porcine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV) by applying bioinformatics methods. The physical and chemical properties, hydrophilicity and hydrophobicity, transmembrane region, signal peptide, phosphorylation and glycosylation sites, epitope, functional domains, and motifs of S proteins of porcine enteric coronaviruses were predicted and analyzed through online software. The results showed that S proteins of TGEV, PEDV, SADS-CoV, and PDCoV all contained transmembrane regions and signal peptide. TGEV S protein contained 139 phosphorylation sites, 24 glycosylation sites, and 53 epitopes. PEDV S protein had 143 phosphorylation sites, 22 glycosylation sites, and 51 epitopes. SADS-CoV S protein had 109 phosphorylation sites, 20 glycosylation sites, and 43 epitopes. PDCoV S protein had 124 phosphorylation sites, 18 glycosylation sites, and 52 epitopes. Moreover, TGEV, PEDV, and PDCoV S proteins all contained two functional domains and two motifs, spike_rec_binding and corona_S2. The corona_S2 consisted of S2 subunit heptad repeat 1 (HR1) and S2 subunit heptad repeat 2 (HR2) region profiles. Additionally, SADS-CoV S protein was predicted to contain only one functional domain, the corona_S2. This analysis of the biological functions of porcine enteric coronavirus spike proteins can provide a theoretical basis for the design of antiviral drugs.
Topics: Alphacoronavirus; Animals; Computational Biology; Coronavirus; Coronavirus Infections; Databases, Genetic; Deltacoronavirus; Epitopes; Porcine epidemic diarrhea virus; Spike Glycoprotein, Coronavirus; Swine; Swine Diseases; Transmissible gastroenteritis virus
PubMed: 34307666
DOI: 10.1155/2021/6689471 -
Viruses May 2023Porcine viral diarrhea is very common in clinical practice and has caused huge losses to the pig industry. Porcine epidemic diarrhea virus (PEDV), porcine rotavirus...
Porcine viral diarrhea is very common in clinical practice and has caused huge losses to the pig industry. Porcine epidemic diarrhea virus (PEDV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are important pathogens of porcine viral diarrhea. Co-infection situations among these three viruses in clinics are common, which increases the difficulty of differential diagnosis. Currently, polymerase chain reaction (PCR) is commonly used to detect pathogens. TaqMan real-time PCR is more sensitive than conventional PCR and has better specificity and accuracy. In this study, a triplex real-time RT-PCR assay based on TaqMan probes was developed for differential detection of PEDV, PoRV, and PDCoV. The triplex real-time RT-PCR assay developed in this study could not detect unrelated pathogens and showed satisfactory specificity, sensitivity, repeatability, and reproducibility with a limit of detection (LOD) of 6.0 × 10 copies/μL. Sixteen clinical samples were used to compare the results of the commercial RT-PCR kit and the triplex RT-PCR for PEDV, PoRV, and PDCoV detection, and the results were completely consistent. A total of 112 piglet diarrhea samples collected from Jiangsu province were next used to study the local prevalence of PEDV, PoRV, and PDCoV. The positive rates of PEDV, PoRV, and PDCoV detected by the triplex real-time RT-PCR were 51.79% (58/112), 59.82% (67/112), and 2.68% (3/112), respectively. The co-infections of PEDV and PoRV were frequent (26/112, 23.21%), followed by the co-infections of PDCoV and PoRV (2/112, 1.79%). This study established a useful tool for simultaneous differentiation of PEDV, PoRV, and PDCoV in practice and provided valuable information on the prevalence of these diarrhea viral pathogens in Jiangsu province.
Topics: Animals; Swine; Porcine epidemic diarrhea virus; Real-Time Polymerase Chain Reaction; Coronavirus Infections; Reverse Transcriptase Polymerase Chain Reaction; Coinfection; Reproducibility of Results; Swine Diseases; Diarrhea; Sensitivity and Specificity
PubMed: 37376539
DOI: 10.3390/v15061238 -
Emerging Infectious Diseases Feb 2020Coronaviruses cause respiratory and gastrointestinal diseases in diverse host species. Deltacoronaviruses (DCoVs) have been identified in various songbird species and in...
Coronaviruses cause respiratory and gastrointestinal diseases in diverse host species. Deltacoronaviruses (DCoVs) have been identified in various songbird species and in leopard cats in China. In 2009, porcine deltacoronavirus (PDCoV) was detected in fecal samples from pigs in Asia, but its etiologic role was not identified until 2014, when it caused major diarrhea outbreaks in swine in the United States. Studies have shown that PDCoV uses a conserved region of the aminopeptidase N protein to infect cell lines derived from multiple species, including humans, pigs, and chickens. Because PDCoV is a potential zoonotic pathogen, investigations of its prevalence in humans and its contribution to human disease continue. We report experimental PDCoV infection and subsequent transmission among poultry. In PDCoV-inoculated chicks and turkey poults, we observed diarrhea, persistent viral RNA titers from cloacal and tracheal samples, PDCoV-specific serum IgY antibody responses, and antigen-positive cells from intestines.
Topics: Animals; Chickens; Coronavirus Infections; Deltacoronavirus; Swine; Swine Diseases; Turkeys; United States
PubMed: 31961296
DOI: 10.3201/eid2602.190346 -
BioRxiv : the Preprint Server For... Apr 2024Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent...
Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.
PubMed: 38617231
DOI: 10.1101/2024.03.27.586411