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Emerging Microbes & Infections Dec 2023Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that has been reported to infect a variety of animals and even humans. Cell-cell fusion has been...
Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that has been reported to infect a variety of animals and even humans. Cell-cell fusion has been identified as an alternative pathway for the cell-to-cell transmission of certain viruses, but the ability of PDCoV to exploit this transmission model, and the relevant mechanisms, have not been fully elucidated. Herein, we provide evidence that cell-to-cell transmission is the main mechanism supporting PDCoV spread in cell culture and that this efficient spread model is mediated by spike glycoprotein-driven cell-cell fusion. We found that PDCoV efficiently spread to non-susceptible cells via cell-to-cell transmission, and demonstrated that functional receptor porcine aminopeptidase N and cathepsins in endosomes are involved in the cell-to-cell transmission of PDCoV. Most importantly, compared with non-cell-to-cell infection, the cell-to-cell transmission of PDCoV was resistant to neutralizing antibodies and immune sera that potently neutralized free viruses. Taken together, our study revealed key characteristics of the cell-to-cell transmission of PDCoV and provided new insights into the mechanism of PDCoV infection.
Topics: Humans; Animals; Swine; Deltacoronavirus; Coronavirus; Antibodies, Neutralizing; Coronavirus Infections; Swine Diseases
PubMed: 37125733
DOI: 10.1080/22221751.2023.2207688 -
Bulletin de L'Academie Nationale de... Aug 2021Coronaviruses are RNA viruses classified into Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Their name comes from their conformation with the...
Coronaviruses are RNA viruses classified into Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Their name comes from their conformation with the observation of spicules forming a sort of crown. Coronaviruses seem to come from bats, and more particularly Alphacoronaviruses and Betacoronaviruses (the genus where zoonoses are observed), while birds are the source of Gammacoronaviruses and Deltacoronaviruses. The first coronavirus identified was that of avian infectious bronchitis in 1931 in the United States, while the first coronaviruses were described in humans only in the 1960s. This is why coronaviruses were mainly known in the veterinary community. Most Alphacoronaviruses are species specific. They can be responsible for serious diseases such as the cat coronavirus, responsible for feline infectious peritonitis, transmissible gastroenteritis (GET) in piglets and porcine epidemic diarrhea (PED), porcine respiratory coronavirus (PRCV). Finally, a deltacoronavirus can be found in both pigs (PD CoV UKU15) and birds.
PubMed: 34108733
DOI: 10.1016/j.banm.2021.05.011 -
Viruses Jul 2023Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), members of the genus Coronavirus, mainly cause acute diarrhea, vomiting and dehydration in...
Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), members of the genus Coronavirus, mainly cause acute diarrhea, vomiting and dehydration in piglets, and thus lead to serious economic losses. In this study, we investigated the effects of nicotinamide (NAM) on PEDV and PDCoV replication and found that NAM treatment significantly inhibited PEDV and PDCoV reproduction. Moreover, NAM plays an important role in replication processes. NAM primarily inhibited PEDV and PDCoV RNA and protein synthesis rather than other processes. Furthermore, we discovered that NAM treatment likely inhibits the replication of PEDV and PDCoV by downregulating the expression of transcription factors through activation of the ERK1/2/MAPK pathway. Overall, this study is the first to suggest that NAM might be not only an important antiviral factor for swine intestinal coronavirus, but also a potential candidate to be evaluated in the context of other human and animal coronaviruses.
Topics: Animals; Humans; Swine; Porcine epidemic diarrhea virus; Niacinamide; Coronavirus; Deltacoronavirus; Coronavirus Infections; Diarrhea; Swine Diseases; Virus Replication
PubMed: 37515276
DOI: 10.3390/v15071591 -
Frontiers in Veterinary Science 2020Deltacoronavirus (DCoV)-the only coronavirus that can infect multiple species of mammals and birds-was initially identified in several avian and mammalian species,... (Review)
Review
Deltacoronavirus (DCoV)-the only coronavirus that can infect multiple species of mammals and birds-was initially identified in several avian and mammalian species, including pigs, in China in 2009-2011. Porcine DCoV has since spread worldwide and is associated with multiple outbreaks of diarrheal disease of variable severity in farmed pigs. In contrast, avian DCoV is being reported in wild birds in different countries without any evidence of disease. The DCoV transboundary nature and the recent discovery of its remarkably broad reactivity with its cellular receptor-aminopeptidase N (APN)-from different species emphasize its epidemiological relevance and necessitate additional research. Further, the ability of porcine DCoV to infect and cause disease in chicks and turkey poults and gnotobiotic calves is suggestive of its increased potential for interspecies transmission or of its avian origin. Whether, porcine DCoVs were initially acquired by one or several mammalian species from birds and whether avian and porcine DCoVs continue co-evolving with frequent spillover events remain to be major unanswered questions. In this review, we will discuss the current information on the prevalence, genetic diversity, and pathogenic potential of porcine and avian DCoVs. We will also analyze the existing evidence of the ongoing interspecies transmission of DCoVs that may provide novel insights into their complex evolution.
PubMed: 33681316
DOI: 10.3389/fvets.2020.626785 -
Viruses Sep 2023Emerging and re-emerging swine coronaviruses (CoVs), including porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea... (Review)
Review
Emerging and re-emerging swine coronaviruses (CoVs), including porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-CoV (SADS-CoV), cause severe diarrhea in neonatal piglets, and CoV infection is associated with significant economic losses for the swine industry worldwide. Reverse genetics systems realize the manipulation of RNA virus genome and facilitate the development of new vaccines. Thus far, five reverse genetics approaches have been successfully applied to engineer the swine CoV genome: targeted RNA recombination, in vitro ligation, bacterial artificial chromosome-based ligation, vaccinia virus -based recombination, and yeast-based method. This review summarizes the advantages and limitations of these approaches; it also discusses the latest research progress in terms of their use for virus-related pathogenesis elucidation, vaccine candidate development, antiviral drug screening, and virus replication mechanism determination.
Topics: Animals; Swine; Coronavirus; Reverse Genetics; Coronavirus Infections; Porcine epidemic diarrhea virus; RNA; Diarrhea; Swine Diseases
PubMed: 37896780
DOI: 10.3390/v15102003 -
Evolutionary Applications Oct 2020Deltacoronavirus is the last identified subfamily genus. Differing from other coronavirus (CoV) genera, which mainly infect birds or mammals, deltacoronaviruses...
Deltacoronavirus is the last identified subfamily genus. Differing from other coronavirus (CoV) genera, which mainly infect birds or mammals, deltacoronaviruses (δ-CoVs) reportedly infect both animal types. Recent studies show that a novel δ-CoV, porcine deltacoronavirus (PDCoV), can also infect calves and chickens with the potential to infect humans, raising the possibility of cross-species transmission of δ-CoVs. Here, we explored the deep phylogenetic history and cross-species transmission of δ-CoVs. Virus-host cophylogenetic analyses showed that δ-CoVs have undergone frequent host switches in birds, and sparrows may serve as the unappreciated hubs for avian to mammal transmission. Our molecular clock analyses show that PDCoV possibly originated in Southeast Asia in the 1990s and that the PDCoV cluster shares a common ancestor with Sparrow-CoV of around 1,810. Our findings contribute valuable insights into the diversification, evolution, and interspecies transmission of δ-CoVs and the origin of PDCoV, providing a model for exploring the relationships of δ-CoVs in birds and mammals.
PubMed: 32837537
DOI: 10.1111/eva.12997 -
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 -
Archives of Virology Nov 2021Porcine deltacoronavirus (PDCoV) is one of the most important enteropathogenic pathogens, and it causes enormous economic losses to the global commercial pork industry.... (Review)
Review
Porcine deltacoronavirus (PDCoV) is one of the most important enteropathogenic pathogens, and it causes enormous economic losses to the global commercial pork industry. PDCoV was initially reported in Hong Kong (China) in 2012 and subsequently emerged in swine herds with diarrhea in Ohio (USA) in 2014. Since then, it has spread to Canada, South Korea, mainland China, and several Southeast Asian countries. Information about the epidemiology, evolution, prevention, and control of PDCoV and its prevalence in China has not been comprehensively reported, especially in the last five years. This review is an update of current information on the general characteristics, epidemiology, geographical distribution, and evolutionary relationships, and the status of PDCoV vaccine development, focusing on the prevalence of PDCoV in China and vaccine research in particular. Together, this information will provide us with a greater understanding of PDCoV infection and will be helpful for establishing new strategies for controlling this virus worldwide.
Topics: Animals; Biological Evolution; China; Coronavirus Infections; Deltacoronavirus; Host Specificity; Phylogeny; Prevalence; Swine; Swine Diseases; Viral Vaccines
PubMed: 34524535
DOI: 10.1007/s00705-021-05226-4 -
Transboundary and Emerging Diseases Jan 2020Increased evidence of porcine deltacoronavirus (PDCoV) causing diarrhoea in pigs has been reported in several countries worldwide. The virus has currently evolved into...
Increased evidence of porcine deltacoronavirus (PDCoV) causing diarrhoea in pigs has been reported in several countries worldwide. The virus has currently evolved into three separated groups including US, China and Southeast Asia (SEA) groups. In Vietnam, PDCoV was first reported in 2015. Based on phylogenetic analyses of spike, membrane and nucleocapsid genes, it is suggested that Vietnam PDCoV is chimeric virus. In the present study, we retrospectively investigated the presence of PDCoV in Vietnam and the full-length genomes of six PDCoV isolates identified in 2014-2016 were further characterized. The results demonstrated that Vietnam PDCoV was first detected as early as 2014. All six Vietnam PDCoV are in the SEA group and further divided into two separated subgroups including SEA-1 and SEA-2. Vietnam PDCoV in SEA-2 was closely related to Thai and Lao PDCoV. Recombination analysis demonstrated that three isolates in SEA-1 were a chimeric virus of which P12_14_VN_0814, the first Vietnam isolate, and US PDCoV isolates were major and minor parents, respectively. The recombination was further evaluated by phylogenetic construction based on 3 recombinant fragments. The first and third fragments, closely related to P12_14_VN_0814, were associated with ORF1a/1b and N genes, respectively. The second fragment, associated with S, E, and M genes, was closely related to US PDCoV isolates. High antigenic and hydrophobic variations were detected in S1 protein. Three-day-old pigs challenged with the chimeric virus displayed clinical diseases and villus atrophy. In conclusion, Vietnam PDCoV is genetically diverse influenced by an external introduction from neighbouring countries. The chimeric Vietnam PDCoV can induce a disease similar to Thai PDCoV.
Topics: Animals; Chimera; Coronavirus; Coronavirus Infections; Diarrhea; Genome, Viral; Phylogeny; Recombination, Genetic; Retrospective Studies; Swine; Swine Diseases; Vietnam; Virulence
PubMed: 31469947
DOI: 10.1111/tbed.13339 -
Viruses Jun 2021The viral family comprises four genera, termed -, and Recombination events have been described in many coronaviruses infecting humans and other animals. However,...
The viral family comprises four genera, termed -, and Recombination events have been described in many coronaviruses infecting humans and other animals. However, formal analysis of the recombination patterns, both in terms of the involved genome regions and the extent of genetic divergence between partners, are scarce. Common methods of recombination detection based on phylogenetic incongruences (e.g., a phylogenetic compatibility matrix) may fail in cases where too many events diminish the phylogenetic signal. Thus, an approach comparing genetic distances in distinct genome regions (pairwise distance deviation matrix) was set up. In alpha, beta, and delta-coronaviruses, a low incidence of recombination between closely related viruses was evident in all genome regions, but it was more extensive between the spike gene and other genome regions. In contrast, avian gammacoronaviruses recombined extensively and exist as a global cloud of genes with poorly corresponding genetic distances in different parts of the genome. Spike, but not other structural proteins, was most commonly exchanged between coronaviruses. Recombination patterns differed between coronavirus genera and corresponded to the modular structure of the spike: recombination traces were more pronounced between spike domains (N-terminal and C-terminal parts of S1 and S2) than within domains. The variability of possible recombination events and their uneven distribution over the genome suggest that compatibility of genes, rather than mechanistic or ecological limitations, shapes recombination patterns in coronaviruses.
Topics: Animals; Birds; Coronavirus; Coronavirus Infections; Evolution, Molecular; Genetic Variation; Genome, Viral; Phylogeny; Recombination, Genetic; Viral Proteins
PubMed: 34209881
DOI: 10.3390/v13071270