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1.
BMC Vet Res ; 18(1): 90, 2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1789121

ABSTRACT

BACKGROUND: Infectious bronchitis virus (IBV) leads to huge economic losses in the poultry industry worldwide. The high levels of mutations of IBV render vaccines partially protective. Therefore, it is urgent to explore an effective antiviral drug or agent. The present study aimed to investigate the in vivo anti-IBV activity of a mixture of plant essential oils (PEO) of cinnamaldehyde (CA) and glycerol monolaurate (GML), designated as Jin-Jing-Zi. RESULTS: The antiviral effects were evaluated by clinical signs, viral loads, immune organ indices, antibody levels, and cytokine levels. The infection rates in the PEO-M (middle dose) and PEO-H (high dose) groups were significantly lower than those in the prevention, positive drug, and PEO-L (low dose) groups. The cure rates in the PEO-M and PEO-H groups were significantly higher than those in the prevention, positive drug, and PEO-L groups, and the PEO-M group had the highest cure rate of 92.31%. The symptom scores and IBV mRNA expression levels were significantly reduced in the PEO-M group. PEO significantly improved the immune organ indices and IBV-specific antibody titers of infected chickens. The anti-inflammatory factor levels of IL-4 and IFN-γ in the PEO-M group maintained high concentrations for a long time. The IL-6 levels in the PEO-M group were lower than those in prevention, positive drug, and PEO-L groups. CONCLUSION: The PEO had remarkable inhibition against IBV and the PEO acts by inhibiting virus multiplication and promoting immune function, suggesting that the PEO has great potential as a novel anti-IBV agent for inhibiting IBV infection.


Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Oils, Volatile , Poultry Diseases , Viral Vaccines , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Chickens , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Plant Oils/pharmacology , Plant Oils/therapeutic use , Poultry Diseases/drug therapy , Poultry Diseases/prevention & control , Viral Vaccines/therapeutic use
2.
J Virol ; 96(6): e0205921, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1788916

ABSTRACT

The Gammacoronavirus infectious bronchitis virus (IBV) is a highly contagious global pathogen prevalent in all types of poultry flocks. IBV is responsible for economic losses and welfare issues in domestic poultry, resulting in a significant risk to food security. IBV vaccines are currently generated by serial passage of virulent IBV field isolates through embryonated hens' eggs. The different patterns of genomic variation accumulated during this process means that the exact mechanism of attenuation is unknown and presents a risk of reversion to virulence. Additionally, the passaging process adapts the virus to replicate in chicken embryos, increasing embryo lethality. Vaccines produced in this manner are therefore unsuitable for in ovo application. We have developed a reverse genetics system, based on the pathogenic IBV strain M41, to identify genes which can be targeted for rational attenuation. During the development of this reverse genetics system, we identified four amino acids, located in nonstructural proteins (nsps) 10, 14, 15, and 16, which resulted in attenuation both in vivo and in ovo. Further investigation highlighted a role of amino acid changes, Pro85Leu in nsp 10 and Val393Leu in nsp 14, in the attenuated in vivo phenotype observed. This study provides evidence that mutations in nsps offer a promising mechanism for the development of rationally attenuated live vaccines against IBV, which have the potential for in ovo application. IMPORTANCE The Gammacoronavirus infectious bronchitis virus (IBV) is the etiological agent of infectious bronchitis, an acute, highly contagious, economically important disease of poultry. Vaccination is achieved using a mixture of live attenuated vaccines for young chicks and inactivated vaccines as boosters for laying hens. Live attenuated vaccines are generated through serial passage in embryonated hens' eggs, an empirical process which achieves attenuation but retains immunogenicity. However, these vaccines have a risk of reversion to virulence, and they are lethal to the embryo. In this study, we identified amino acids in the replicase gene which attenuated IBV strain M41, both in vivo and in ovo. Stability assays indicate that the attenuating amino acids are stable and unlikely to revert. The data in this study provide evidence that specific modifications in the replicase gene offer a promising direction for IBV live attenuated vaccine development, with the potential for in ovo application.


Subject(s)
Coronavirus Infections , Gammacoronavirus , Infectious bronchitis virus , Poultry Diseases , Viral Vaccines , Amino Acids , Animals , Chick Embryo , Chickens , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Female , Poultry , Vaccines, Attenuated/genetics
3.
Vet Microbiol ; 267: 109391, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1778497

ABSTRACT

Protein tyrosine phosphatase non-receptor type 14 (PTPN14) is a member of the protein tyrosine phosphatase (PTP) family which is a potential tumor suppressor. PTPs modulate the cellular level of tyrosine phosphorylation under normal and pathological conditions. Porcine epidemic diarrhea virus (PEDV) is one of the most important pathogens in the swine industry. Our previous membrane proteomics results showed that PTPN14 was markedly upregulated in PEDV-infected Vero cells. However, its biological roles in PEDV infection have not yet been investigated. In this study, we reported PTPN14 functions as a novel regulator of signal transducer and activator of transcription 3 (STAT3) phosphorylation during PEDV infection. Firstly, PTPN14 was markedly upregulated in PEDV-infected Vero cells with the decrease of STAT3 phosphorylation. Knockdown of PTPN14 or phosphatase inhibitor treatment promoted PEDV proliferation and increased the phosphorylation of STAT3 in Vero cells. On the contrary, overexpression of PTPN14 inhibits viral infection in Vero cells. Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus. Collectively, our results indicate that PTPN14 plays a negative role in regulating STAT3 activation in PEDV infected Vero cells and demonstrate another layer of regulation in PEDV infection.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Animals , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/veterinary , Porcine epidemic diarrhea virus/physiology , Protein Tyrosine Phosphatases/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Swine , Tyrosine/metabolism , Vero Cells
4.
Transbound Emerg Dis ; 69(2): 396-412, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1774900

ABSTRACT

A limited understanding of the transmission dynamics of swine disease is a significant obstacle to prevent and control disease spread. Therefore, understanding between-farm transmission dynamics is crucial to developing disease forecasting systems to predict outbreaks that would allow the swine industry to tailor control strategies. Our objective was to forecast weekly porcine epidemic diarrhoea virus (PEDV) outbreaks by generating maps to identify current and future PEDV high-risk areas, and simulating the impact of control measures. Three epidemiological transmission models were developed and compared: a novel epidemiological modelling framework was developed specifically to model disease spread in swine populations, PigSpread, and two models built on previously developed ecosystems, SimInf (a stochastic disease spread simulations) and PoPS (Pest or Pathogen Spread). The models were calibrated on true weekly PEDV outbreaks from three spatially related swine production companies. Prediction accuracy across models was compared using the receiver operating characteristic area under the curve (AUC). Model outputs had a general agreement with observed outbreaks throughout the study period. PoPS had an AUC of 0.80, followed by PigSpread with 0.71, and SimInf had the lowest at 0.59. Our analysis estimates that the combined strategies of herd closure, controlled exposure of gilts to live viruses (feedback) and on-farm biosecurity reinforcement reduced the number of outbreaks. On average, 76% to 89% reduction was seen in sow farms, while in gilt development units (GDU) was between 33% to 61% when deployed to sow and GDU farms located in probabilistic high-risk areas. Our multi-model forecasting approach can be used to prioritize surveillance and intervention strategies for PEDV and other diseases potentially leading to more resilient and healthier pig production systems.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Disease Outbreaks/prevention & control , Disease Outbreaks/veterinary , Ecosystem , Farms , Female , Swine , Swine Diseases/epidemiology , Swine Diseases/prevention & control
5.
Int J Mol Sci ; 23(6)2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1760651

ABSTRACT

PDCoV is an emerging enteropathogenic coronavirus that mainly causes acute diarrhea in piglets, seriously affecting pig breeding industries worldwide. To date, the molecular mechanisms of PDCoV-induced immune and inflammatory responses or host responses in LLC-PK cells in vitro are not well understood. HSP90 plays important roles in various viral infections. In this study, HSP90AB1 knockout cells (HSP90AB1KO) were constructed and a comparative transcriptomic analysis between PDCoV-infected HSP90AB1WT and HSP90AB1KO cells was conducted using RNA sequencing to explore the effect of HSP90AB1 on PDCoV infection. A total of 1295 and 3746 differentially expressed genes (DEGs) were identified in PDCoV-infected HSP90AB1WT and HSP90AB1KO cells, respectively. Moreover, most of the significantly enriched pathways were related to immune and inflammatory response-associated pathways upon PDCoV infection. The DEGs enriched in NF-κB pathways were specifically detected in HSP90AB1WT cells, and NF-κB inhibitors JSH-23, SC75741 and QNZ treatment reduced PDCoV infection. Further research revealed most cytokines associated with immune and inflammatory responses were upregulated during PDCoV infection. Knockout of HSP90AB1 altered the upregulated levels of some cytokines. Taken together, our findings provide new insights into the host response to PDCoV infection from the transcriptome perspective, which will contribute to illustrating the molecular basis of the interaction between PDCoV and HSP90AB1.


Subject(s)
Coronavirus Infections/veterinary , Deltacoronavirus , Gene Expression Profiling , HSP90 Heat-Shock Proteins/genetics , Immunity/genetics , Swine Diseases/etiology , Transcriptome , Animals , Computational Biology/methods , Disease Susceptibility , Gene Knockdown Techniques , Gene Ontology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , NF-kappa B/metabolism , Swine
6.
Emerg Microbes Infect ; 11(1): 1010-1013, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1750052

ABSTRACT

Equine coronavirus (ECoV) was first identified in the USA and has been previously described in several countries. In order to test the presence of ECoV in China, we collected 51 small intestinal samples from donkey foals with diarrhoea from a donkey farm in Shandong Province, China between August 2020 and April 2021. Two samples tested positive for ECoV and full-length genome sequences were successfully obtained using next-generation sequencing, one of which was further confirmed by Sanger sequencing. The two strains shared 100% sequence identity at the scale of whole genome. Bioinformatics analyses further showed that the two Chinese strains represent a novel genetic variant of ECoV and shared the highest sequence identity of 97.05% with the first identified ECoV strain - NC99. In addition, it may be a recombinant, with the recombination region around the NS2 gene. To our knowledge, this is the first documented report of ECoV in China, highlighting its risk to horse/donkey breeding. In addition, its potential risk to public health also warrants further investigation.


Subject(s)
Betacoronavirus 1 , Coronavirus Infections , Horse Diseases , Animals , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Diarrhea/veterinary , Equidae , Horse Diseases/epidemiology , Horses , Phylogeny
7.
Acta Virol ; 64(2): 264-267, 2020.
Article in English | MEDLINE | ID: covidwho-1718101

ABSTRACT

The members of coronavirus family are facultative pathogens of birds and mammals, including men. From their first isolation 60 years ago, they caused smaller or larger epidemics mainly originating from China. The most recent pandemic quickly spreading worldwide has affected over 2,000,000 people. Keywords: coronavirus; epidemic; single strand vRNA.


Subject(s)
Coronavirus Infections , Coronavirus , Animals , Birds , COVID-19 , China/epidemiology , Coronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Mammals , Pandemics , Pneumonia, Viral/epidemiology
8.
Viruses ; 14(2)2022 02 17.
Article in English | MEDLINE | ID: covidwho-1703374

ABSTRACT

Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are urgently needed. In this study, we characterize the antiviral effects of two high-sulfated glycosaminoglycan (GAG) derivatives against SARS-CoV-2 and bovine coronaviruses (BCoV), which are both members of the Betacoronavirus genus. The investigated compounds are based on hyaluronan (HA) and chondroitin sulfate (CS) and exhibit a strong inhibitory effect against both CoVs. Yield assays were performed using BCoV-infected PT cells in the presence and absence of the compounds. While the high-sulfated HA (sHA3) led to an inhibition of viral growth early after infection, high-sulfated CS (sCS3) had a slightly smaller effect. Time of addition assays, where sHA3 and sCS3 were added to PT cells before, during or after infection, demonstrated an inhibitory effect during all phases of infection, whereas sHA3 showed a stronger effect even after virus absorbance. Furthermore, attachment analyses with prechilled PT cells revealed that virus attachment is not blocked. In addition, sHA3 and sCS3 inactivated BCoV by stable binding. Analysis by quantitative real-time RT PCR underlines the high potency of the inhibitors against BCoV, as well as B.1-lineage, Alpha and Beta SARS-CoV-2 viruses. Taken together, these results demonstrated that the two high-sulfated GAG derivatives exhibit low cytotoxicity and represent promising candidates for an anti-CoV therapy.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections/veterinary , Coronavirus, Bovine/drug effects , Glycosaminoglycans/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19/drug therapy , Cattle , Cell Line , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Coronavirus Infections/drug therapy , Glycosaminoglycans/chemistry , Glycosaminoglycans/metabolism , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Sulfates/chemistry , Sulfates/pharmacology , Virus Attachment/drug effects
9.
PLoS One ; 17(2): e0263582, 2022.
Article in English | MEDLINE | ID: covidwho-1677590

ABSTRACT

The membrane protein M of the Porcine Epidemic Diarrhea Virus (PEDV) is the most abundant component of the viral envelope. The M protein plays a central role in the morphogenesis and assembly of the virus through protein interactions of the M-M, M-Spike (S) and M-nucleocapsid (N) type. The M protein is known to induce protective antibodies in pigs and to participate in the antagonistic response of the cellular antiviral system coordinated by the type I and type III interferon pathways. The 3D structure of the PEDV M protein is still unknown. The present work exposes a predicted 3D model of the M protein generated using the Robetta protocol. The M protein model is organized into a transmembrane and a globular region. The obtained 3D model of the PEDV M protein was compared with 3D models of the SARS-CoV-2 M protein created using neural networks and with initial machine learning-based models created using trRosetta. The 3D model of the present study predicted four linear B-cell epitopes (RSVNASSGTG and KHGDYSAVSNPSALT peptides are noteworthy), six discontinuous B-cell epitopes, forty weak binding and fourteen strong binding T-cell epitopes in the CV777 M protein. A high degree of conservation of the epitopes predicted in the PEDV M protein was observed among different PEDV strains isolated in different countries. The data suggest that the M protein could be a potential candidate for the development of new treatments or strategies that activate protective cellular mechanisms against viral diseases.


Subject(s)
Coronavirus Infections/virology , Coronavirus M Proteins/chemistry , Porcine epidemic diarrhea virus/chemistry , Swine Diseases/virology , Swine/virology , Amino Acid Sequence , Animals , Coronavirus Infections/immunology , Coronavirus Infections/veterinary , Coronavirus M Proteins/immunology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Models, Molecular , Porcine epidemic diarrhea virus/immunology , Protein Conformation , Swine Diseases/immunology
10.
Viruses ; 14(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1674829

ABSTRACT

Coronaviruses (CoV) are divided into the genera α-CoVs, ß-CoVs, γ-CoVs and δ-CoVs. Of these, α-CoVs and ß-CoVs are solely capable of causing infections in humans, resulting in mild to severe respiratory symptoms. Bats have been identified as natural reservoir hosts for CoVs belonging to these two genera. Consequently, research on bat populations, CoV prevalence in bats and genetic characterization of bat CoVs is of special interest to investigate the potential transmission risks. We present the genome sequence of a novel α-CoV strain detected in rectal swab samples of Miniopterus fuliginosus bats from a colony in the Wavul Galge cave (Koslanda, Sri Lanka). The novel strain is highly similar to Miniopterus bat coronavirus 1, an α-CoV located in the subgenus of Minunacoviruses. Phylogenetic reconstruction revealed a high identity of the novel strain to other α-CoVs derived from Miniopterus bats, while human-pathogenic α-CoV strains like HCoV-229E and HCoV-NL63 were more distantly related. Comparison with selected bat-related and human-pathogenic strains of the ß-CoV genus showed low identities of ~40%. Analyses of the different genes on nucleotide and amino acid level revealed that the non-structural ORF1a/1b are more conserved among α-CoVs and ß-CoVs, while there are higher variations in the structural proteins known to be important for host specificity. The novel strain was named batCoV/MinFul/2018/SriLanka and had a prevalence of 50% (66/130) in rectal swab samples and 58% (61/104) in feces samples that were collected from Miniopterus bats in Wavul Galge cave. Based on the differences between strain batCoV/MinFul/2018/SriLanka and human-pathogenic α-CoVs and ß-CoVs, we conclude that there is a rather low transmission risk to humans. Further studies in the Wavul Galge cave and at other locations in Sri Lanka will give more detailed information about the prevalence of this virus.


Subject(s)
Alphacoronavirus/genetics , Alphacoronavirus/isolation & purification , Chiroptera/virology , Coronavirus Infections/veterinary , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Genome, Viral , Alphacoronavirus/classification , Animals , Caves/virology , Coronavirus Infections/virology , Evolution, Molecular , Female , Male , Phylogeny , Sequence Analysis, DNA , Sri Lanka
11.
Front Immunol ; 12: 826882, 2021.
Article in English | MEDLINE | ID: covidwho-1674339

ABSTRACT

Swine enteric coronaviruses (SECoVs) including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine deltacoronavirus (PDCoV), account for the majority of lethal watery diarrhea in neonatal pigs and pose significant economic and public health burdens in the world. While the three SECoVs primarily infect intestinal epithelia in vivo and cause similar clinical signs, there are evident discrepancies in their cellular tropism and pathogenicity. However, the underlying mechanisms to cause the differences remain unclear. Herein, we employed porcine enteroids that are a physiologically relevant model of the intestine to assess the host epithelial responses following infection with the three SECoVs (PEDV, TGEV, and PDCoV). Although SECoVs replicated similarly in jejunal enteroids, a parallel comparison of transcriptomics datasets uncovered that PEDV and TGEV infection induced similar transcriptional profiles and exhibited a more pronounced response with more differentially expressed genes (DEGs) in jejunal enteroids compared with PDCoV infection. Notably, TGEV and PDCoV induced high levels of type I and III IFNs and IFN-stimulated gene (ISG) responses, while PEDV displayed a delayed peak and elicited a much lesser extent of IFN responses. Furthermore, TGEV and PDCoV instead of PEDV elicited a substantial upregulation of antigen-presentation genes and T cell-recruiting chemokines in enteroids. Mechanistically, we demonstrated that IFNs treatment markedly elevated the expression of NOD-like receptor (NLR) family NLRC5 and major histocompatibility complex class I (MHC-I) molecules. Together, our results indicate unique and common viral strategies for manipulating the global IFN responses and antigen presentation utilized by SECoVs, which help us a better understanding of host-SECoVs interactions.


Subject(s)
Antigen Presentation/immunology , Coronavirus Infections/veterinary , Gene Expression Regulation , Interferons/metabolism , Porcine epidemic diarrhea virus/physiology , Swine Diseases/etiology , Swine Diseases/metabolism , Animals , Gastroenteritis, Transmissible, of Swine/etiology , Gastroenteritis, Transmissible, of Swine/metabolism , Gastroenteritis, Transmissible, of Swine/pathology , Gene Expression Profiling , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Swine , Swine Diseases/pathology , Transmissible gastroenteritis virus
12.
Vet Microbiol ; 266: 109333, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1629002

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an enteropathogen found in many pig producing countries. It can cause acute diarrhea, vomiting, dehydration, and death in newborn piglets, seriously affecting the development of pig breeding industries. To date, our knowledge of the pathogenesis of PDCoV and its interactions with host cell factors remains incomplete. Using Co-IP coupled with LC/MS-MS, we identified 67 proteins that potentially interact with PDCoV in LLC-PK1 cells; five of the identified proteins were chosen for further evaluation (IMMT, STAT1, XPO5, PIK3AP1, and TMPRSS11E). Five LLC-PK1 cell lines, each with one of the genes of interest knocked down, were constructed using CRISPR/cas9. In these knockdown cells lines, only STAT1KD resulted in a significantly greater virus yield. Knockdown of the remaining four genes resulted, to varying degrees, in a lower virus yield that wild-type LLC-PK1 cells. The absence of STAT1 did not significantly affect the attachment of PDCoV to cells, but did result in increased viral internalization. Additionally, PDCoV infection stimulated expression of interferon stimulated genes (ISGs) downstream of STAT1 (IFIT1, IFIT2, RADS2, ISG15, MX1, and OAS1) while knockdown of STAT1 resulted in a greater than 80 % decrease in the expression of all six ISGs. Our findings show that STAT1 interacts with PDCoV, and plays a negative regulatory role in PDCoV infection.


Subject(s)
Coronavirus Infections , Swine Diseases , Animals , Coronavirus Infections/veterinary , Interferons , LLC-PK1 Cells , Swine , Virus Internalization
13.
Ecohealth ; 18(4): 421-428, 2021 12.
Article in English | MEDLINE | ID: covidwho-1590480

ABSTRACT

We investigated the prevalence of coronaviruses in 44 bats from four families in northeastern Eswatini using high-throughput sequencing of fecal samples. We found evidence of coronaviruses in 18% of the bats. We recovered full or near-full-length genomes from two bat species: Chaerephon pumilus and Afronycteris nana, as well as additional coronavirus genome fragments from C. pumilus, Epomophorus wahlbergi, Mops condylurus, and Scotophilus dinganii. All bats from which we detected coronaviruses were captured leaving buildings or near human settlements, demonstrating the importance of continued surveillance of coronaviruses in bats to better understand the prevalence, diversity, and potential risks for spillover.


Subject(s)
Chiroptera , Coronavirus Infections , Coronavirus , Metagenomics , Animals , Chiroptera/virology , Coronavirus/genetics , Coronavirus Infections/veterinary , Eswatini , Genetic Variation , Genome, Viral , Phylogeny
14.
Viruses ; 14(1)2021 12 31.
Article in English | MEDLINE | ID: covidwho-1580397

ABSTRACT

Mammal-associated coronaviruses have a long evolutionary history across global bat populations, which makes them prone to be the most likely ancestral origins of coronavirus-associated epidemics and pandemics globally. Limited coronavirus research has occurred at the junction of Europe and Asia, thereby investigations in Georgia are critical to complete the coronavirus diversity map in the region. We conducted a cross-sectional coronavirus survey in bat populations at eight locations of Georgia, from July to October of 2014. We tested 188 anal swab samples, remains of previous pathogen discovery studies, for the presence of coronaviruses using end-point pan-coronavirus RT-PCR assays. Samples positive for a 440 bp amplicon were Sanger sequenced to infer coronavirus subgenus or species through phylogenetic reconstructions. Overall, we found a 24.5% positive rate, with 10.1% for Alphacoronavirus and 14.4% for Betacoronavirus. Albeit R. euryale, R. ferrumequinum, M. blythii and M. emarginatus were found infected with both CoV genera, we could not rule out CoV co-infection due to limitation of the sequencing method used and sample availability. Based on phylogenetic inferences and genetic distances at nucleotide and amino acid levels, we found one putative new subgenus and three new species of Alphacoronavirus, and two new species of Betacoronavirus.


Subject(s)
Chiroptera/virology , Coronavirus Infections/veterinary , Coronavirus/genetics , Animals , Base Sequence , Coronavirus/classification , Coronavirus/isolation & purification , Coronavirus Infections/virology , Cross-Sectional Studies , Genetic Variation , Geography , Georgia (Republic) , Phylogeny , RNA, Viral/genetics , Viral Proteins/genetics
15.
Viruses ; 14(1)2021 12 30.
Article in English | MEDLINE | ID: covidwho-1576960

ABSTRACT

Canine coronavirus (CCoV) is widespread among the dog population and causes gastrointestinal disorders, and even fatal cases. As the zoonotic transmission of viruses from animals to humans has become a worldwide concern nowadays, it is necessary to screen free-roaming dogs for their common pathogens due to their frequent interaction with humans. We conducted a cross-sectional study to detect and characterize the known and novel Corona, Filo, Flavi, and Paramyxoviruses in free-roaming dogs in Bangladesh. Between 2009-10 and 2016-17, we collected swab samples from 69 dogs from four districts of Bangladesh, tested using RT-PCR and sequenced. None of the samples were positive for Filo, Flavi, and Paramyxoviruses. Only three samples (4.3%; 95% CI: 0.9-12.2) tested positive for Canine Coronavirus (CCoV). The CCoV strains identified were branched with strains of genotype CCoV-II with distinct distances. They are closely related to CCoVs from the UK, China, and other CoVs isolated from different species, which suggests genetic recombination and interspecies transmission of CCoVs. These findings indicate that CCoV is circulating in dogs of Bangladesh. Hence, we recommend future studies on epidemiology and genetic characterization with full-genome sequencing of emerging coronaviruses in companion animals in Bangladesh.


Subject(s)
Coronavirus Infections/veterinary , Coronavirus, Canine/genetics , Coronavirus, Canine/isolation & purification , Dog Diseases/epidemiology , Animals , Bangladesh/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Coronavirus, Canine/classification , Cross-Sectional Studies , Dog Diseases/virology , Dogs , Female , Genotype , Male , Phylogeny , Viral Proteins/genetics
16.
Vet Microbiol ; 264: 109299, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1559479

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an emerging porcine enteric coronavirus that causes severe diarrhea in piglets and results in serious economic losses. There are no effective vaccines and antiviral drugs to prevent and treat PDCoV infection currently. Griffithsin (GRFT) is a lectin with potent antiviral activity against enveloped viruses because of its ability to specifically bind N-linked high-mannose oligosaccharides. GRFT has been reported to possess antiviral activity against severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and porcine epidemic diarrhea virus (PEDV). Here, we first confirmed the antiviral activity of GRFT against PDCoV in vitro. The infected cells (%) and virus titers were significantly decreased at concentration 1 µg/mL or above of GRFT. Time-course experiments revealed that GRFT inhibits PDCoV infection at the adsorption and penetration step. GRFT binding to PDCoV spike (S) protein on the surface wraps the virus and blocks its entry. The outstanding antiviral potency indicates that GRFT has the potential value as a candidate drug for the prevention and treatment of PDCoV infection.


Subject(s)
Deltacoronavirus , Plant Lectins , Animals , Antiviral Agents/pharmacology , Cell Culture Techniques/veterinary , Coronavirus Infections/drug therapy , Coronavirus Infections/veterinary , Deltacoronavirus/drug effects , Plant Lectins/pharmacology , Swine , Swine Diseases/drug therapy
17.
Viruses ; 13(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1555020

ABSTRACT

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in nursing piglets. Studies showed that PDCoV uses porcine aminopeptidase N (pAPN) as an entry receptor, but the infection of pAPN-knockout cells or pigs with PDCoV revealed that pAPN might be not a critical functional receptor, implying there exists an unidentified receptor involved in PDCoV infection. Herein, we report that sialic acid (SA) can act as an attachment receptor for PDCoV invasion and facilitate its infection. We first demonstrated that the carbohydrates destroyed on the cell membrane using NaIO4 can alleviate the susceptibility of cells to PDCoV. Further study showed that the removal of SA, a typical cell-surface carbohydrate, could influence the PDCoV infectivity to the cells significantly, suggesting that SA was involved in the infection. The results of plaque assay and Western blotting revealed that SA promoted PDCoV infection by increasing the number of viruses binding to SA on the cell surface during the adsorption phase, which was also confirmed by atomic force microscopy at the microscopic level. In in vivo experiments, we found that the distribution levels of PDCoV and SA were closely relevant in the swine intestine, which contains huge amount of trypsin. We further confirmed that SA-binding capacity to PDCoV is related to the pre-treatment of PDCoV with trypsin. In conclusion, SA is a novel attachment receptor for PDCoV infection to enhance its attachment to cells, which is dependent on the pre-treatment of trypsin on PDCoV. This study paves the way for dissecting the mechanisms of PDCoV-host interactions and provides new strategies to control PDCoV infection.


Subject(s)
Deltacoronavirus/physiology , N-Acetylneuraminic Acid/metabolism , Receptors, Virus/metabolism , Trypsin/metabolism , Virus Attachment , Animals , Carbohydrates , Cell Line , Cell Membrane/metabolism , Cell Membrane/virology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Deltacoronavirus/drug effects , Host-Pathogen Interactions , Intestines/metabolism , Intestines/virology , Periodic Acid/pharmacology , Swine , Swine Diseases/virology , Trypsin/pharmacology
18.
Adv Exp Med Biol ; 1313: 85-97, 2021.
Article in English | MEDLINE | ID: covidwho-1473148

ABSTRACT

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that circulates in dromedary camels and sporadically transmit into humans, subsequently resulting in community and nosocomial cases. The viral infection in humans has a range of disease severity from asymptomatic to severe pneumonia and death, whereas the infection in camels is usually asymptomatic. There is no approved antiviral therapy or vaccine for MERS-CoV infections although there have been a number of therapeutic and vaccine candidates under development, for both humans and camels. To date, there has been limited research on the immune responses and pathogenesis of MERS-CoV in both humans and camels. Here, this chapter is focused on MERS-CoV specific immunity in different species with some details regarding the various animal models.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Animals , Camelus , Coronavirus Infections/veterinary , Humans , Immunity
19.
Viruses ; 13(11)2021 10 29.
Article in English | MEDLINE | ID: covidwho-1488763

ABSTRACT

In the last two decades, several coronavirus (CoV) interspecies jumping events have occurred between bats and other animals/humans, leading to major epidemics/pandemics and high fatalities. The SARS epidemic in 2002/2003 had a ~10% fatality. The discovery of SARS-related CoVs in horseshoe bats and civets and genomic studies have confirmed bat-to-civet-to-human transmission. The MERS epidemic that emerged in 2012 had a ~35% mortality, with dromedaries as the reservoir. Although CoVs with the same genome organization (e.g., Tylonycteris BatCoV HKU4 and Pipistrellus BatCoV HKU5) were also detected in bats, there is still a phylogenetic gap between these bat CoVs and MERS-CoV. In 2016, 10 years after the discovery of Rhinolophus BatCoV HKU2 in Chinese horseshoe bats, fatal swine disease outbreaks caused by this virus were reported in southern China. In late 2019, an outbreak of pneumonia emerged in Wuhan, China, and rapidly spread globally, leading to >4,000,000 fatalities so far. Although the genome of SARS-CoV-2 is highly similar to that of SARS-CoV, patient zero and the original source of the pandemic are still unknown. To protect humans from future public health threats, measures should be taken to monitor and reduce the chance of interspecies jumping events, either occurring naturally or through recombineering experiments.


Subject(s)
COVID-19/virology , Chiroptera/virology , Coronavirus Infections/virology , Coronavirus/physiology , Host Adaptation , Severe Acute Respiratory Syndrome/virology , Alphacoronavirus/genetics , Alphacoronavirus/physiology , Animals , COVID-19/transmission , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Host Specificity , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/physiology , SARS Virus/genetics , SARS Virus/physiology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/veterinary
20.
Infect Dis Poverty ; 10(1): 128, 2021 Oct 24.
Article in English | MEDLINE | ID: covidwho-1482013

ABSTRACT

BACKGROUND: Coronaviruses can be isolated from bats, civets, pangolins, birds and other wild animals. As an animal-origin pathogen, coronavirus can cross species barrier and cause pandemic in humans. In this study, a deep learning model for early prediction of pandemic risk was proposed based on the sequences of viral genomes. METHODS: A total of 3257 genomes were downloaded from the Coronavirus Genome Resource Library. We present a deep learning model of cross-species coronavirus infection that combines a bidirectional gated recurrent unit network with a one-dimensional convolution. The genome sequence of animal-origin coronavirus was directly input to extract features and predict pandemic risk. The best performances were explored with the use of pre-trained DNA vector and attention mechanism. The area under the receiver operating characteristic curve (AUROC) and the area under precision-recall curve (AUPR) were used to evaluate the predictive models. RESULTS: The six specific models achieved good performances for the corresponding virus groups (1 for AUROC and 1 for AUPR). The general model with pre-training vector and attention mechanism provided excellent predictions for all virus groups (1 for AUROC and 1 for AUPR) while those without pre-training vector or attention mechanism had obviously reduction of performance (about 5-25%). Re-training experiments showed that the general model has good capabilities of transfer learning (average for six groups: 0.968 for AUROC and 0.942 for AUPR) and should give reasonable prediction for potential pathogen of next pandemic. The artificial negative data with the replacement of the coding region of the spike protein were also predicted correctly (100% accuracy). With the application of the Python programming language, an easy-to-use tool was created to implements our predictor. CONCLUSIONS: Robust deep learning model with pre-training vector and attention mechanism mastered the features from the whole genomes of animal-origin coronaviruses and could predict the risk of cross-species infection for early warning of next pandemic.


Subject(s)
Coronavirus Infections , Coronavirus , Pandemics , Animals , Coronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Deep Learning , Humans , Models, Statistical , Risk Assessment/methods
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