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Virus Research Dec 2016Porcine deltacoronavirus (PDCoV) (family Coronaviridae, genus Deltacoronavirus) is a novel swine enteropathogenic coronavirus that causes acute diarrhea/vomiting,... (Review)
Review
Porcine deltacoronavirus (PDCoV) (family Coronaviridae, genus Deltacoronavirus) is a novel swine enteropathogenic coronavirus that causes acute diarrhea/vomiting, dehydration and mortality in seronegative neonatal piglets. PDCoV diarrhea was first reported in the US in early 2014, concurrently with co-circulation of porcine epidemic diarrhea virus (PEDV) (family Coronaviridae, genus Alphacoronavirus). The origin of PDCoV in pigs and also its sudden emergence or route of introduction into the US still remains unclear. In the US, since 2013-2014, the newly emerged PDCoV and PEDV have spread nationwide, causing a high number of pig deaths and significant economic impacts. The current US PDCoV strains are enteropathogenic and infect villous epithelial cells of the entire small and large intestines although the jejunum and ileum are the primary sites of infection. Similar to PEDV infections, PDCoV infections also cause acute, severe atrophic enteritis accompanied by transient viremia (viral RNA) that leads to severe diarrhea and/or vomiting, followed by dehydration as the potential cause of death in nursing piglets. At present, differential diagnosis of PDCoV, PEDV, and transmissible gastroenteritis virus (TGEV) is essential to control viral diarrheas in US swine. Cell culture-adapted US PDCoV (TC-PDCoV) strains have been isolated and propagated by us and in several other laboratories. TC-PDCoV strains will be useful to develop serologic assays and to evaluate if serial cell-culture passage attenuates TC-PDCoV as a potential vaccine candidate strain. A comprehensive understanding of the pathogenesis and epidemiology of epidemic PDCoV strains is currently needed to prevent and control the disease in affected regions and to develop an effective vaccine. This review focuses on the etiology, cell culture isolation and propagation, molecular epidemiology, disease mechanisms and pathogenesis of PDCoV infection.
Topics: Animals; Cell Culture Techniques; Coronavirus; Coronavirus Infections; Cross Reactions; Genome, Viral; Immunity; Molecular Epidemiology; Phylogeny; Swine; Swine Diseases; Virulence; Virus Cultivation
PubMed: 27086031
DOI: 10.1016/j.virusres.2016.04.009 -
Nature Communications Mar 2022Porcine deltacoronavirus (PDCoV) can experimentally infect a variety of animals. Human infection by PDCoV has also been reported. Consistently, PDCoV can use...
Porcine deltacoronavirus (PDCoV) can experimentally infect a variety of animals. Human infection by PDCoV has also been reported. Consistently, PDCoV can use aminopeptidase N (APN) from different host species as receptors to enter cells. To understand this broad receptor usage and interspecies transmission of PDCoV, we determined the crystal structures of the receptor binding domain (RBD) of PDCoV spike protein bound to human APN (hAPN) and porcine APN (pAPN), respectively. The structures of the two complexes exhibit high similarity. PDCoV RBD binds to common regions on hAPN and pAPN, which are different from the sites engaged by two alphacoronaviruses: HCoV-229E and porcine respiratory coronavirus (PRCoV). Based on structure guided mutagenesis, we identified conserved residues on hAPN and pAPN that are essential for PDCoV binding and infection. We report the detailed mechanism for how a deltacoronavirus recognizes homologous receptors and provide insights into the cross-species transmission of PDCoV.
Topics: Animals; Coronavirus; Coronavirus 229E, Human; Coronavirus Infections; Deltacoronavirus; Humans; Spike Glycoprotein, Coronavirus; Swine
PubMed: 35304871
DOI: 10.1038/s41467-022-29062-5 -
Molecular Biology and Evolution Sep 2020The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and interlineage recombination and higher virus genetic diversity in the Chinese lineages compared with the USA lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, whereas the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in CoVs emergence.
Topics: Animals; Biological Evolution; China; Coronavirus; Coronavirus Infections; Genetic Variation; Genome, Viral; Genomics; Humans; Models, Molecular; Molecular Epidemiology; Open Reading Frames; Phylogeny; Phylogeography; Protein Structure, Secondary; Recombination, Genetic; Selection, Genetic; Spike Glycoprotein, Coronavirus; Swine; Swine Diseases; Viral Proteins
PubMed: 32407507
DOI: 10.1093/molbev/msaa117 -
Journal of Virology Dec 2022Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, not only causes diarrhea in piglets but also possesses the potential to infect humans. To...
Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, not only causes diarrhea in piglets but also possesses the potential to infect humans. To better understand host-virus genetic dependencies and find potential therapeutic targets for PDCoV, we used a porcine single-guide RNA (sgRNA) lentivirus library to screen host factors related to PDCoV infection in LLC-PK1 cells. The solute carrier family 35 member A1 (SLC35A1), a key molecule in the sialic acid (SA) synthesis pathway, was identified as a host factor required for PDCoV infection. A knockout of SLC35A1 caused decreases in the amounts of cell surface sialic acid (SA) and viral adsorption; meanwhile, trypsin promoted the use of SA in PDCoV infection. By constructing and assessing a series of recombinant PDCoV strains with the deletion or mutation of possible critical domain or amino acid residues for SA binding in the S1 N-terminal domain, we found that S T182 might be a PDCoV SA-binding site. However, the double knockout of SLC35A1 and amino peptidase N (APN) could not block PDCoV infection completely. Additionally, we found that different swine enteric coronaviruses, including transmissible gastroenteritis coronavirus, porcine epidemic diarrhea virus, and swine acute diarrhea syndrome coronavirus, are differentially dependent on SA. Overall, our study uncovered a collection of host factors that can be exploited as drug targets against PDCoV infection and deepened our understanding of the relationship between PDCoV and SA. Identifying the host factors required for replication will be helpful to uncover the pathogenesis mechanisms and develop antivirals against the emerging coronavirus porcine deltacoronavirus (PDCoV). Herein, we performed a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout screen, the results of which revealed that the solute carrier family 35 member A1 (SLC35A1) is a host factor required for PDCoV infection that acts by regulating cell surface sialic acid (SA). We also identified the T182 site in the N-terminal domain of PDCoV S1 subunit as being associated with the SA-binding site and found that trypsin promotes the use of cell surface SA by PDCoV. Furthermore, different swine enteric coronaviruses use SLC35A1 differently for infection. This is the first study to screen host factors required for PDCoV replication using a genome-wide CRISPR-Cas9 functional knockout, thereby providing clues for developing antiviral drugs against PDCoV infection.
Topics: Animals; Humans; Adsorption; Coronavirus; Coronavirus Infections; CRISPR-Cas Systems; N-Acetylneuraminic Acid; Nucleotide Transport Proteins; Swine; Swine Diseases; Trypsin; Host Microbial Interactions; Protein Domains; Binding Sites
PubMed: 36453883
DOI: 10.1128/jvi.01626-22 -
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 -
Journal of Virology Apr 2012Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified...
Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus.
Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.
Topics: Animals; Base Sequence; Bird Diseases; Birds; Cats; Chiroptera; Coronaviridae; Coronaviridae Infections; Coronavirus; Dogs; Evolution, Molecular; Genome, Viral; Haplorhini; Humans; Mammals; Molecular Sequence Data; Phylogeny; Rodentia; Swine; Viral Proteins
PubMed: 22278237
DOI: 10.1128/JVI.06540-11 -
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 -
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 -
Current Opinion in Virology Feb 2019Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are emerging/reemerging coronaviruses... (Review)
Review
Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are emerging/reemerging coronaviruses (CoVs). They cause acute gastroenteritis in neonatal piglets. Sequence analyses suggest that PEDV and SADS-CoV may have originated from bat CoVs and PDCoV from a sparrow CoV, reaffirming the interspecies transmission of CoVs. The clinical signs and pathogenesis of the three viruses are similar. Necrosis of infected intestinal epithelial cells occurs, causing villous atrophy that results in malabsorptive diarrhea. The severe diarrhea and vomiting may lead to dehydration and death of piglets. Natural infection induces protective immunity, but there is no cross-protection among the three viruses. Besides strict biosecurity measures, individual vaccines are needed for each virus for disease prevention and control.
Topics: Animals; Coronavirus; Coronavirus Infections; Diarrhea; Genome, Viral; Humans; Phylogeny; Porcine epidemic diarrhea virus; Swine; Swine Diseases
PubMed: 30654269
DOI: 10.1016/j.coviro.2018.12.001 -
Frontiers in Veterinary Science 2021The recent experience with SARS-COV-2 has raised our alarm about the cross-species transmissibility of coronaviruses and the emergence of new coronaviruses. Knowledge of... (Review)
Review
The recent experience with SARS-COV-2 has raised our alarm about the cross-species transmissibility of coronaviruses and the emergence of new coronaviruses. Knowledge of this family of viruses needs to be constantly updated. Porcine (PDCoV), a newly emerging member of the genus in the family , is a swine enteropathogen that causes diarrhea in pigs and may lead to death in severe cases. Since PDCoV diarrhea first broke out in the United States in early 2014, PDCoV has been detected in many countries, such as South Korea, Japan and China. More importantly, PDCoV can also infect species other than pigs, and infections have even been reported in children, highlighting its potential for cross-species transmission. A thorough and systematic knowledge of the epidemiology and pathogenesis of PDCoV will not only help us control PDCoV infection, but also enable us to discover the common cellular pathways and key factors of coronaviruses. In this review, we summarize the current knowledge on the prevalence, pathogenicity and infection dynamics, pathogenesis and immune evasion strategies of PDCoV. The existing anti-PDCoV strategies and corresponding mechanisms of PDCoV infection are also introduced, aiming to provide suggestions for the prevention and treatment of PDCoV and zoonotic diseases.
PubMed: 35097055
DOI: 10.3389/fvets.2021.811187