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Viruses Apr 2023Porcine deltacoronavirus (PDCoV) causes diarrhea and vomiting in neonatal piglets worldwide and has the potential for cross-species transmission. Therefore, virus-like...
Porcine deltacoronavirus (PDCoV) causes diarrhea and vomiting in neonatal piglets worldwide and has the potential for cross-species transmission. Therefore, virus-like particles (VLPs) are promising vaccine candidates because of their safety and strong immunogenicity. To the best of our knowledge, the present study reported for the first time the generation of PDCoV VLPs using a baculovirus expression vector system, and electron micrograph analyses revealed that PDCoV VLPs appeared as spherical particles with a diameter similar to that of the native virions. Furthermore, PDCoV VLPs effectively induced mice to produce PDCoV-specific IgG and neutralizing antibodies. In addition, VLPs could stimulate mouse splenocytes to produce high levels of cytokines IL-4 and IFN-γ. Moreover, the combination of PDCoV VLPs and Freund's adjuvant could improve the level of the immune response. Together, these data showed that PDCoV VLPs could effectively elicit humoral and cellular immunity in mice, laying a solid foundation for developing VLP-based vaccines to prevent PDCoV infections.
Topics: Animals; Mice; Swine; Baculoviridae; Antibodies, Neutralizing; Coronavirus; Immunity; Swine Diseases; Coronavirus Infections
PubMed: 37243181
DOI: 10.3390/v15051095 -
Virus Research Dec 2016Porcine deltacoronavirus (PDCoV) was first reported in Hong Kong, China in 2012 and reported in United States swine in February 2014. PDCoV has subsequently been... (Review)
Review
Porcine deltacoronavirus (PDCoV) was first reported in Hong Kong, China in 2012 and reported in United States swine in February 2014. PDCoV has subsequently been detected in South Korea, mainland China, and Thailand. PDCoV has been experimentally confirmed to cause diarrhea in inoculated pigs and need to be differentially diagnosed from porcine epidemic diarrhea virus and transmissible gastroenteritis virus in the field. Rapid diagnosis is critical for the implementation of efficient control strategies against PDCoV. Developing high-quality diagnostic methods and understanding PDCoV infection dynamics to collect appropriate specimens at the appropriate time window are important to obtain reliable diagnostic results. Among the virological methods, PDCoV-specific RT-PCR remains the method of choice for the detection of PDCoV; immunohistochemistry combined with hematoxylin and eosin staining has also been commonly used to examine histopathological lesions caused by PDCoV. Serological assays can provide information about previous exposure to PDCoV and also determine antibody responses to infection or vaccination. Prevalence of PDCoV is lower compared to that of PEDV. However, among PDCoV-positive samples, co-infection with other enteric pathogen e.g. PEDV is common. It is also important to understand molecular epidemiology of PDCoV and genetic relationships of global PDCoVs. This review discusses PDCoV infection dynamics and appropriate sample collection for diagnostic testing, the commonly used virological and serological methods for PDCoV diagnosis, prevalence and genetic evolution of PDCoVs.
Topics: Animals; Coronavirus; Coronavirus Infections; Diarrhea; Evolution, Molecular; Genome, Viral; Genomics; Global Health; Molecular Diagnostic Techniques; Phylogeny; Prevalence; Serologic Tests; Swine; Swine Diseases
PubMed: 27270129
DOI: 10.1016/j.virusres.2016.05.028 -
Frontiers in Microbiology 2023Coinfection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) is common in pig farms, but there is currently no effective vaccine to prevent...
Developing a multi-epitope vaccine candidate to combat porcine epidemic diarrhea virus and porcine deltacoronavirus co-infection by employing an immunoinformatics approach.
Coinfection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) is common in pig farms, but there is currently no effective vaccine to prevent this co-infection. In this study, we used immunoinformatics tools to design a multi-epitope vaccine against PEDV and PDCoV co-infection. The epitopes were screened through a filtering pipeline comprised of antigenic, immunogenic, toxic, and allergenic properties. A new multi-epitope vaccine named , comprising cytotoxic T lymphocyte-, helper T lymphocyte-, and B cell epitopes, was constructed. To enhance immunogenicity, the TLR2 agonist Pam2Cys and the TLR4 agonist RS09 were added to . Molecular docking and dynamics simulation were performed to reveal the stable interactions between and TLR2 as well as TLR4. Additionally, the immune stimulation prediction indicated that could stimulate T and B lymphocytes to induce a robust immune response. Finally, to ensure the expression of the vaccine protein, the sequence of was optimized and further performed cloning. These studies suggest that has the potential to be a vaccine candidate against PEDV and PDCoV co-infection as well as a new strategy for interrupting the spread of both viruses.
PubMed: 38075906
DOI: 10.3389/fmicb.2023.1295678 -
MBio Dec 2021Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs (ncRNAs) present in various tissues and cells. However, the functions of most circRNAs have not...
Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs (ncRNAs) present in various tissues and cells. However, the functions of most circRNAs have not been verified experimentally. Here, using deltacoronavirus as a model, differentially expressed circRNAs in cells with or without deltacoronavirus infection were analyzed by RNA sequencing to characterize the cellular responses to RNA virus infection. More than 57,000 circRNA candidates were detected, and seven significantly dysregulated circRNAs were quantitated by real-time reverse transcription-PCR. We discovered a previously unidentified circRNA derived from the gene, named circTNFAIP3, which is distributed and expressed widely in various tissues. RNA viruses, including deltacoronaviruses, rather than DNA viruses tend to activate the expression of endogenous circTNFAIP3. Overexpression of circTNFAIP3 promoted deltacoronavirus replication by reducing the apoptosis, while silencing of circTNFAIP3 inhibited deltacoronavirus replication by enhancing the apoptosis. In summary, our work provides useful circRNA-related information to facilitate investigation of the underlying mechanism of deltacoronavirus infection and identifies a novel circTNFAIP3 that promotes deltacoronavirus replication via regulating apoptosis. CircRNAs, a new class of ncRNAs, play important roles in cell growth, neural development, carcinogenesis, and anticarcinogenesis. Porcine deltacoronavirus is an emerging enteropathogenic coronavirus that causes diarrhea, but the role of host circRNAs in regulating its infection is unknown. Here, we performed expression profiling of circRNAs in mock- and deltacoronavirus- infected cells and identified the novel differentially expressed circular RNA circTNFAIP3. We demonstrate that circTNFAIP3 promotes deltacoronavirus replication by inhibiting apoptosis. Our findings first illustrate that circRNA can act as an apoptosis negative regulator during RNA virus infection and help to explore the underlying mechanism of deltacoronavirus infection.
Topics: Apoptosis; Cell Line; Deltacoronavirus; Gene Expression Profiling; HEK293 Cells; High-Throughput Nucleotide Sequencing; Host Microbial Interactions; Humans; RNA, Circular; Sequence Analysis, RNA; Tumor Necrosis Factor alpha-Induced Protein 3; Virus Replication
PubMed: 34781747
DOI: 10.1128/mBio.02984-21 -
Microbiology Spectrum Aug 2023Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered emerging alphacoronavirus. SADS-CoV shares over 90% genome sequence identity with bat...
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered emerging alphacoronavirus. SADS-CoV shares over 90% genome sequence identity with bat alphacoronavirus HKU2. SADS-CoV was associated with severe diarrhea and high mortality rates in piglets. Accurate serological diagnosis of SADS-CoV infection is key in managing the emerging SADS-CoV. However, thus far there have been no effective antibody-based diagnostic tests for diagnose of SADS-CoV exposure. Here, monoclonal antibody (MAb) 6E8 against SADS-CoV N protein accurately recognized SADS-CoV infection. Then, MAb 6E8 was utilized as a blocking antibody to develop blocking ELISA (bELISA). We customized the rN coating antigen with concentration 0.25 μg/mL. According to receiver operator characteristic curve analysis, the cutoff value of the bELISA was determined as 38.19% when the max Youden index was 0.955, and specificity was 100%, and sensitivity was 95.5%. Specificity testing showed that there was no cross-reactivity with other serum positive swine enteric coronaviruses, such as porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), porcine rotavirus (PoRV), and porcine sapelovirus (PSV). In conclusion, we customized a novel and high-quality blocking ELISA for detection of SADS-CoV infection, and the current bELISA will be linked to a clinical and epidemiological assessment of SADS-CoV infection. SADS-CoV was reported to be of high potential for dissemination among various of host species. Accurate serological diagnosis of SADS-CoV infection is key in managing the emerging SADS-CoV. However, thus far there have been no effective antibody-based diagnostic tests for diagnose of SADS-CoV exposure. We customed a novel and high-quality bELISA assay for detection of SADS-CoV N protein antibodies, and the current bELISA will be linked to a clinical and epidemiological assessment of SADS-CoV infection.
Topics: Animals; Swine; Chiroptera; Coronavirus Infections; Alphacoronavirus; Enzyme-Linked Immunosorbent Assay; Diarrhea; Antibodies, Monoclonal; Swine Diseases
PubMed: 37272819
DOI: 10.1128/spectrum.03930-22 -
Microbiology Spectrum Aug 2023Coronaviruses (CoVs) are enveloped viruses with a large RNA genome (26 to 32 kb) and are classified into four genera: , , and . CoV infections cause respiratory,...
Coronaviruses (CoVs) are enveloped viruses with a large RNA genome (26 to 32 kb) and are classified into four genera: , , and . CoV infections cause respiratory, enteric, and neurologic disorders in mammalian and avian species. In 2019, Oryx leucoryx animals suffered from severe hemorrhagic diarrhea and high morbidity rates. Upon initial diagnosis, we found that the infected animals were positive for coronavirus by pancoronavirus reverse transcriptase RT-PCR. Next, we detected the presence of CoV particles in these samples by electron microscopy and immunohistochemistry. CoV was isolated and propagated on the HRT-18G cell line, and its full genome was sequenced. Full-genome characterization and amino acid comparisons of this viral agent demonstrated that this virus is an evolutionarily distinct belonging to the subgenus and the species. Furthermore, we found that it is most similar to the subspecies dromedary camel coronavirus HKU23 by phylogenetic analysis. Here, we present the first report of isolation and characterization of associated with enteric disease in CoVs cause enteric and respiratory infections in humans and animal hosts. The ability of CoVs to cross interspecies barriers is well recognized, as emphasized by the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of novel CoV strains and surveillance of CoVs in both humans and animals are relevant and important to global health. In this study, we isolated and characterized a newly identified that causes enteric disease in a wild animal, (the Arabian oryx). This work is the first report describing CoV infection in and provides insights into its origin.
Topics: Animals; Humans; Phylogeny; COVID-19; SARS-CoV-2; Animals, Wild; Birds; Mammals
PubMed: 37428095
DOI: 10.1128/spectrum.04848-22 -
Frontiers in Microbiology 2022Host's innate immunity is the front-line defense against viral infections, but some viruses have evolved multiple strategies for evasion of antiviral innate immunity.... (Review)
Review
Host's innate immunity is the front-line defense against viral infections, but some viruses have evolved multiple strategies for evasion of antiviral innate immunity. The porcine enteric coronaviruses (PECs) consist of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), transmissible gastroenteritis coronavirus (TGEV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV), which cause lethal diarrhea in neonatal pigs and threaten the swine industry worldwide. PECs interact with host cells to inhibit and evade innate antiviral immune responses like other coronaviruses. Moreover, the immune escape of porcine enteric coronaviruses is the key pathogenic mechanism causing infection. Here, we review the most recent advances in the interactions between viral and host's factors, focusing on the mechanisms by which viral components antagonize interferon (IFN)-mediated innate antiviral immune responses, trying to shed light on new targets and strategies effective for controlling and eliminating porcine enteric coronaviruses.
PubMed: 35237253
DOI: 10.3389/fmicb.2022.845137 -
BMC Veterinary Research Sep 2023Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes enteric diseases in pigs leading to substantial financial losses within the industry. The absence of...
Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes enteric diseases in pigs leading to substantial financial losses within the industry. The absence of commercial vaccines and limited research on PDCoV vaccines presents significant challenges. Therefore, we evaluated the safety and immunogenicity of recombinant pseudorabies virus (PRV) rPRVXJ-delgE/gI/TK-S through intranasal mucosal immunization in weaned piglets and SPF mice. Results indicated that rPRVXJ-delgE/gI/TK-S safely induced PDCoV S-specific and PRV gB-specific antibodies in piglets, with levels increasing 7 days after immunization. Virus challenge tests demonstrated that rPRVXJ-delgE/gI/TK-S effectively improved piglet survival rates, reduced virus shedding, and alleviated clinical symptoms and pathological damage. Notably, the recombinant virus reduced anti-inflammatory and pro-inflammatory responses by regulating IFN-γ, TNF-α, and IL-1β secretion after infection. Additionally, rPRVXJ-delgE/gI/TK-S colonized target intestinal segments infected with PDCoV, stimulated the secretion of cytokines by MLVS in mice, stimulated sIgA secretion in different intestinal segments of mice, and improved mucosal immune function. HE and AB/PAS staining confirmed a more complete intestinal mucosal barrier and a significant increase in goblet cell numbers after immunization. In conclusion, rPRVXJ-delgE/gI/TK-S exhibits good immunogenicity and safety in mice and piglets, making it a promising candidate vaccine for PDCoV.
Topics: Animals; Mice; Swine; Immunity, Mucosal; Administration, Intranasal; COVID-19; Vaccines, Synthetic; Intestines; Antibodies, Viral; Swine Diseases
PubMed: 37741960
DOI: 10.1186/s12917-023-03739-5 -
Pathogens (Basel, Switzerland) Jan 2022Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus of swine that causes acute diarrhoea, vomiting, dehydration and mortality in seronegative... (Review)
Review
Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus of swine that causes acute diarrhoea, vomiting, dehydration and mortality in seronegative neonatal piglets. PDCoV was first reported in Hong Kong in 2012 and its etiological features were first characterized in the United States in 2014. Currently, PDCoV is a concern due to its broad host range, including humans. Chickens, turkey poults, and gnotobiotic calves can be experimentally infected by PDCoV. Therefore, as discussed in this review, a comprehensive understanding of the origin, evolution, cross-species transmission and zoonotic potential of epidemic PDCoV strains is urgently needed.
PubMed: 35056027
DOI: 10.3390/pathogens11010079 -
Virus Research May 2023A variety of swine enteric coronaviruses (SECoVs) have emerged and are prevalent in pig populations, including porcine epidemic diarrhea virus (PEDV), transmissible...
A variety of swine enteric coronaviruses (SECoVs) have emerged and are prevalent in pig populations, including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome (SADS)-CoV, a newly identified bat-origin CoV with zoonotic potential. Unfortunately, available traditional, inactivated and attenuated SECoV vaccines are of limited efficacy against the variants currently circulating in most pig populations. In this study, we evaluated the role of host factor heat shock protein 90 (Hsp90) as an antiviral target against SECoVs, exemplified by SADS-CoV. Pharmacological inhibition of Hsp90 diminished SADS-CoV replication significantly in porcine and human cell lines, and also decreased replication of SADS-CoV in a porcine intestinal enteroid model. Further mechanistic experiments revealed that both porcine and human isoforms of Hsp90 interact with the SADS-CoV nucleocapsid (N) protein, and inhibition of Hsp90 resulted in autophagic degradation of N protein. Moreover, we linked Hsp90 to virus-induced cellular pyroptosis, as SADS-CoV was found to trigger caspase-1/gasdermin-d-mediated pyroptotic cell death, which was mitigated by inhibition of Hsp90. Finally, we demonstrated that Hsp90 also associated with N proteins and was involved in propagation of PEDV, PDCoV and TGEV. This study thus extends our understanding of immune responses to SADS-CoV infection and offers a new potential therapeutic option against four SECoVs.
Topics: Animals; Humans; Alphacoronavirus; Antiviral Agents; Coronavirus Infections; Heat-Shock Proteins; Porcine epidemic diarrhea virus; Swine; Swine Diseases; Transmissible gastroenteritis virus; HSP90 Heat-Shock Proteins
PubMed: 36963723
DOI: 10.1016/j.virusres.2023.199103