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Scientific Reports Nov 2022Coronaviruses of the genera Gammacoronavirus and Deltacoronavirus are globally widespread and circulate primarily in wild and domestic birds. Prior studies have...
Coronaviruses of the genera Gammacoronavirus and Deltacoronavirus are globally widespread and circulate primarily in wild and domestic birds. Prior studies have established frequently occurring crossover events from avian to mammalian reservoirs. However, there is limited understanding of the diversity and geographical distribution of coronaviruses among birds. In this study, the surveillance of coronaviruses in birds in Russia during 2020 revealed the presence of coronaviruses in 12% of samples from birds. Targeted NGS approach was used for the evaluation of genetic diversity based on RdRp gene. While gammacoronviruses were found in both wild birds and poultry, deltacoronaviruses were found in wild birds only and represent the first detections for Russia. A number of cases with the simultaneous detection of gamma- and deltacoronaviruses in one bird was reported. The results of this study highlight the importance of further research concerning the spread and diversity of coronaviruses among birds within and migrating throughout the territory of Russia across the globe.
Topics: Animals; Gammacoronavirus; Deltacoronavirus; Poultry; Coronavirus; Birds; Animals, Wild; Coronavirus Infections; Mammals; Influenza in Birds; Phylogeny
PubMed: 36371465
DOI: 10.1038/s41598-022-23925-z -
Microbiology Spectrum Dec 2022Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus in pigs, is one of the major pathogens for lethal watery diarrhea in piglets and poses a...
Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus in pigs, is one of the major pathogens for lethal watery diarrhea in piglets and poses a threat to public health because of its potential for interspecies transmission to humans. 25-Hydroxycholesterol (25HC), a derivative of cholesterol, exhibits multiple potential modulating host responses to pathogens, including viruses and bacteria, as well as pathogen-induced inflammation, while its antiviral effect on PDCoV and how it mediates the biological process of host cells to counter against infections remain poorly understood. Here, we thoroughly explored the antiviral effect of 25HC on PDCoV infection and tried to elucidate the underlying mechanisms. 25HC showed no toxic effect in LLC-PK1 cells and exerted antiviral ability against PDCoV infection . The viral cycle and time-of-addition analyses showed that 25HC mainly restricted the early and middle periods of the PDCoV postentry stage to inhibit infection. 25HC regulated disordered cholesterol metabolism induced by PDCoV infection and stimulated interferon-related lipid droplet accumulation. Transforming growth factor β1 (TGF-β1), screened by bioinformatic analyses, seemed to play an important role in PDCoV infection and was downregulated by 25HC. One interesting finding is that inhibition of TGF-β1 with the inhibitor asiaticoside exhibited a similar antiviral capacity to 25HC and demonstrated regulation of cholesterol metabolism. Taking all of the findings together, we verified the antiviral effect of 25HC on PDCoV through interference with cholesterol metabolism, which may be related to its suppression of TGFβ1. As an emerging enteropathogenic coronavirus in pigs, porcine deltacoronavirus (PDCoV) causes giant economic loss in the pig industry because of lethal diarrhea and possesses the potential for transmission from animals to humans. Several pieces of evidence have suggested the antiviral potential of cholesterol-25-hydroxylase and importance of cholesterol in viral infection. This study reports that 25-hydroxycholesterol (25HC) significantly restricted PDCoV infection through modulation of cholesterol metabolism, and we identified that lipid droplets play important roles in interferon response against virus infection. Moreover, this study identified the importance of TGF-β1 in CoV infection by bioinformatic analysis and verified that the inhibition of TGF-β1 showed anti-PDCoV capacity. Moreover, we uncovered the relationship between TGF-β and cholesterol metabolism initially. Given that the importance of cholesterol in viral infection, 25HC has a great potential to treat PDCoV infection and TGF-β1 can be a crucial antiviral target.
Topics: Animals; Antiviral Agents; Coronavirus; Coronavirus Infections; Diarrhea; Interferons; Swine; Swine Diseases; Transforming Growth Factor beta1
PubMed: 36314946
DOI: 10.1128/spectrum.02198-22 -
Viruses Oct 2022Pig diarrhea is a universal problem in the process of pig breeding, which seriously affects the development of the pig industry. Porcine enteric coronaviruses (PECoVs)... (Review)
Review
Pig diarrhea is a universal problem in the process of pig breeding, which seriously affects the development of the pig industry. Porcine enteric coronaviruses (PECoVs) are common pathogens causing diarrhea in pigs, currently including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV). With the prosperity of world transportation and trade, the spread of viruses is becoming wider and faster, making it even more necessary to prevent PECoVs. In this paper, the host factors required for the efficient replication of these CoVs and the compounds that exhibit inhibitory effects on them were summarized to promote the development of drugs against PECoVs. This study will be also helpful in discovering general host factors that affect the replication of CoVs and provide references for the prevention and treatment of other CoVs.
Topics: Swine; Animals; Coronavirus; Coronavirus Infections; Swine Diseases; Porcine epidemic diarrhea virus; Diarrhea
PubMed: 36298772
DOI: 10.3390/v14102217 -
Viruses Sep 2022This study characterized the susceptibility and dynamic of porcine deltacoronavirus infection in grower pigs under experimental conditions using a combination of...
This study characterized the susceptibility and dynamic of porcine deltacoronavirus infection in grower pigs under experimental conditions using a combination of syndromic and laboratory assessments. Seven-week-old conventional pigs ( = 24) were randomly distributed into PDCoV- ( = 12) and mock-inoculated ( = 12) groups. Serum was collected at -7, 0, 3, 7, 10, 14, 17, 21, 28, 35, and 42 days post-inoculation (DPI) to evaluate viremia (RT-qPCR) and antibody response (S1-based ELISA). Viral shedding and potential infectivity were determined using pen-based oral fluids and feces collected every other day between DPI 0 and 42. Pigs showed no clinical signs or viremia throughout the study. Active virus shedding was detected in feces (6-22 DPI) and oral fluids (2-30 DPI), peaking at DPI 10. IgG was first detected at DPI 10, being statistically significant after DPI 14 and increasing thereafter, coinciding with the progressive resolution of the infection. Likewise, a significant increase in proinflammatory IL-12 was detected between DPI 10 and 21 in PDCoV-inoculated pigs, which could enhance innate resistance to PDCoV infection. This study demonstrated that active surveillance based on systematic sampling and laboratory testing combining molecular and serological tools is critical for the accurate detection of subclinical circulation of PDCoV in pigs after weaning.
Topics: Animals; Asymptomatic Infections; Coronavirus Infections; Immunoglobulin G; Interleukin-12; Swine; Swine Diseases; Viremia
PubMed: 36298699
DOI: 10.3390/v14102144 -
Advanced Science (Weinheim,... Dec 2022Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which...
Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which urgently calls for effective broad-spectrum antivirals. RNA-dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan-coronaviral therapeutic target. Herein, based on cryo-electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block SARS-CoV-2 RdRp, thus inhibiting SARS-CoV-2 replication in both cellular and mouse infection models. GOS also acts as a potent inhibitor against the SARS-CoV-2 variant of concern (VOC) and exerts same inhibitory effects toward mutated RdRps of VOCs as the RdRp of the original SARS-CoV-2. Moreover, that the RdRp inhibitor GOS has broad-spectrum anti-coronavirus activity against alphacoronaviruses (porcine epidemic diarrhea virus and swine acute diarrhea syndrome coronavirus), betacoronaviruses (SARS-CoV-2), gammacoronaviruses (avian infectious bronchitis virus), and deltacoronaviruses (porcine deltacoronavirus) is showed. The findings demonstrate that GOS may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and other coronavirus outbreaks.
Topics: Animals; Humans; Mice; COVID-19; Cryoelectron Microscopy; Gossypol; Pandemics; SARS-CoV-2; Swine; COVID-19 Drug Treatment; Coronavirus Infections; Coronavirus RNA-Dependent RNA Polymerase
PubMed: 36266926
DOI: 10.1002/advs.202203499 -
BMC Veterinary Research Oct 2022Swine acute diarrhea syndrome coronavirus (SADS-CoV) causes acute vomiting and diarrhea in piglets, leading to significant financial losses for the pig industry....
BACKGROUND
Swine acute diarrhea syndrome coronavirus (SADS-CoV) causes acute vomiting and diarrhea in piglets, leading to significant financial losses for the pig industry. Recombinase polymerase amplification (RPA) is a rapid nucleic acid amplification technology used under constant temperature conditions. The study established a real-time reverse transcription (RT)-RPA assay for early diagnosis of SADS-CoV. RESULTS: The detection limit of the real-time RT-RPA was 74 copies/µL of SADS-CoV genomic standard recombinant plasmid in 95% of cases. The assay was performed in less than 30 min and no cross-reactions were observed with eight other common viruses that affect swine, including classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), pseudo rabies virus (PRV), swine influenza virus (SIV), seneca valley virus (SVA), transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV). The coefficient of variation (C.V.) values of the two standards dilutions and three positive clinical sample ranged from 2.95% to 4.71%. A total of 72 clinical fecal samples from swine with diarrheal symptoms were analyzed with the developed RT-RPA and quantitative RT-PCR. There was 98.61% agreement between the RT-RPA and the quantitative real-time PCR results.
CONCLUSIONS
These results indicated that the developed RT-RPA assay had good specificity, sensitivity, stability and repeatability. The study successfully established a broadly reactive RT-RPA assay for SADS-CoV detection.
Topics: Alphacoronavirus; Animals; Coronavirus Infections; Diarrhea; Nucleic Acids; Real-Time Polymerase Chain Reaction; Recombinases; Sensitivity and Specificity; Swine; Swine Diseases
PubMed: 36221092
DOI: 10.1186/s12917-022-03465-4 -
Virus Research Dec 2022Porcine deltacoronavirus (PDCoV) and porcine epidemic diarrhoea virus (PEDV) are the main porcine enteric coronaviruses that cause severe diarrhoea in piglets, posing...
Porcine deltacoronavirus (PDCoV) and porcine epidemic diarrhoea virus (PEDV) are the main porcine enteric coronaviruses that cause severe diarrhoea in piglets, posing huge threat to the swine industry. Our previous study verified that the co-infection of PDCoV and PEDV is common in natural swine infections and obviously enhances the disease severity in piglets. However, the effects of co-infection of PDCoV and PEDV on intestinal microbial community are unknown. In current study, the microbial composition and diversity in the colon of piglets were analyzed. Our results showed that both of PDCoV and PEDV were mainly distributed in the small intestines and caused severe damage of ileum but not colon in the co-inoculated piglets. Furthermore, we observed that PDCoV and PEDV co-infection alters the gut microbiota composition at the phylum, family and genus levels. The abundance of Mitsuokella and Collinsella at genus level were significantly increased in PDCoV-PEDV co-infection piglets. Spearman's correlation analysis further suggested that there existed strong positive correlation between Mitsuokella and TNF-α, IL-6 and IL-8 secretion, these two factors may together aggravating the small intestine pathological lesions. These results proved there existed obvious correlation between the disease severity caused by PDCoV-PEDV co-infection and intestinal microbial community.
Topics: Animals; Swine; Porcine epidemic diarrhea virus; Gastrointestinal Microbiome; Coinfection; Swine Diseases; Coronavirus Infections
PubMed: 36198372
DOI: 10.1016/j.virusres.2022.198954 -
Veterinary Microbiology Nov 2022Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). Although they facilitate local...
Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, we found that interleukin-8 (IL-8) was upregulated by PDCoV infection. We then demonstrated that PDCoV E protein induced IL-8 production and that the TM domain and the C-terminal domain of the E protein were important for IL-8 production. Subsequently, we showed here that deleting the AP-1 and NF-κB binding motif in porcine IL-8 promoter abrogated its activation, suggesting that IL-8 expression was dependent on AP-1 and NF-κB. Furthermore, PDCoV E induced IL-8 production, which was also dependent on the NF-κB pathway through activating nuclear factor p65 phosphorylation and NF-κB inhibitor alpha (IκBα) protein phosphorylation, as well as inducing the nuclear translocation of p65, eventually resulting in the promotion of IL-8 production. PDCoV E also activated c-fos and c-jun, both of which are members of the AP-1 family. These findings provide new insights into the molecular mechanisms of PDCoV-induced IL-8 production and help us further understand the pathogenesis of PDCoV infection.
Topics: Swine; Animals; NF-kappa B; NF-KappaB Inhibitor alpha; Interleukin-6; Transcription Factor AP-1; Interleukin-8; SARS-CoV-2; COVID-19; Cytokines; Antiviral Agents; Swine Diseases
PubMed: 36181744
DOI: 10.1016/j.vetmic.2022.109553 -
Frontiers in Immunology 2022Porcine Deltacoronavirus (PDCoV), an enveloped positive-strand RNA virus that causes respiratory and gastrointestinal diseases, is widely spread worldwide, but there is...
Porcine Deltacoronavirus (PDCoV), an enveloped positive-strand RNA virus that causes respiratory and gastrointestinal diseases, is widely spread worldwide, but there is no effective drug or vaccine against it. This study investigated the optimal Selenium Nano-Particles (SeNPs) addition concentration (2 - 10 μg/mL) and the mechanism of PDCoV effect on ST (Swine Testis) cell apoptosis, the antagonistic effect of SeNPs on PDCoV. The results indicated that 4 μg/mL SeNPs significantly decreased PDCoV replication on ST cells. SeNPs relieved PDCoV-induced mitochondrial division and antagonized PDCoV-induced apoptosis decreasing Cyt C release and Caspase 9 and Caspase 3 activation. The above results provided an idea and experimental basis associated with anti-PDCoV drug development and clinical use.
Topics: Animals; Apoptosis; Coronavirus; Coronavirus Infections; Male; Mitochondrial Dynamics; Selenium; Swine; Swine Diseases
PubMed: 36081520
DOI: 10.3389/fimmu.2022.972499 -
International Journal of Molecular... Aug 2022Since the beginning of the 21st century, humans have experienced three coronavirus pandemics, all of which were transmitted to humans via animals. Recent studies have...
Historical Evolutionary Dynamics and Phylogeography Analysis of Transmissible Gastroenteritis Virus and Porcine Deltacoronavirus: Findings from 59 Suspected Swine Viral Samples from China.
Since the beginning of the 21st century, humans have experienced three coronavirus pandemics, all of which were transmitted to humans via animals. Recent studies have found that porcine deltacoronavirus (PDCoV) can infect humans, so swine enteric coronavirus (SeCoV) may cause harm through cross-species transmission. Transmissible gastroenteritis virus (TGEV) and PDCoV have caused tremendous damage and loss to the pig industry around the world. Therefore, we analyzed the genome sequence data of these two SeCoVs by evolutionary dynamics and phylogeography, revealing the genetic diversity and spatiotemporal distribution characteristics. Maximum likelihood and Bayesian inference analysis showed that TGEV could be divided into two different genotypes, and PDCoV could be divided into four main lineages. Based on the analysis results inferred by phylogeography, we inferred that TGEV might originate from America, PDCoV might originate from Asia, and different migration events had different migration rates. In addition, we also identified positive selection sites of spike protein in TGEV and PDCoV, indicating that the above sites play an essential role in promoting membrane fusion to achieve adaptive evolution. In a word, TGEV and PDCoV are the past and future of SeCoV, and the relatively smooth transmission rate of TGEV and the increasing transmission events of PDCoV are their respective transmission characteristics. Our results provide new insights into the evolutionary characteristics and transmission diversity of these SeCoVs, highlighting the potential for cross-species transmission of SeCoV and the importance of enhanced surveillance and biosecurity measures for SeCoV in the context of the COVID-19 epidemic.
Topics: Animals; Bayes Theorem; COVID-19; Deltacoronavirus; Humans; Phylogeography; Swine; Swine Diseases; Transmissible gastroenteritis virus
PubMed: 36077190
DOI: 10.3390/ijms23179786