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1.
Vaccine ; 40(31): 4211-4219, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1882606

ABSTRACT

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in pigs of various ages, especially in suckling piglets, and there are no effective measures to prevent and control PDCoV currently. In this study, two adjuvants Al(OH)3 and ODN2395 working through different mechanisms were used to prepare inactivated PDCoV vaccines, and the immune effects of PDCoV inactivated vaccines were assessed in mice. From the results, we found that both PDCoV/Al(OH)3 vaccine and PDCoV/2395 vaccine could induce IgG and neutralizing antibodies with high levels in mice. At the same time, cytokines of IFN-γ, IL-4 and chemokine ligand of CXCL13 in serum were significantly increased after immunization, and reached the highest levels in PDCoV/2395 vaccine group, which suggested that PDCoV/2395 could promote the production of both Th1 and Th2 polarized cytokines. In addition, histopathological observations showed that vaccination helped mice resist PDCoV infection. These results indicated that both the two inactivated vaccines have good immune effects. Moreover, the PDCoV/2395 vaccine worked better than the PDCoV/Al(OH)3 vaccine for PDCoV/2395 having the good ability to induce both humoral and cellular immunogenicity. The PDCoV/2395 inactivated vaccine developed in this study might be an effective tool for the prevention of PDCoV infection.


Subject(s)
COVID-19 , Swine Diseases , Animals , Cytokines , Deltacoronavirus , Mice , Swine , Vaccines, Inactivated
2.
Int J Mol Sci ; 23(11)2022 May 31.
Article in English | MEDLINE | ID: covidwho-1869642

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is a burdensome coronavirus for the global pig industry. Although its fecal-oral route has been well-recognized, increasing evidence suggests that PEDV can also spread through airborne routes, indicating that the infection may also occur in the respiratory tract. N6-methyladenosine (m6A) has been known to regulate viral replication and host immunity, yet its regulatory role and molecular mechanism regarding PEDV infection outside the gastrointestinal tract remain unexplored. In this study, we demonstrate that PEDV can infect porcine lung tissue and the 3D4/21 alveolar macrophage cell line, and the key m6A demethylase ALKBH5 is remarkably induced after PEDV infection. Interestingly, the disruption of ALKBH5 expression remarkably increases the infection's capacity for PEDV. Transcriptome profiling identified dozens of putative targets of ALKBH5, including GAS6, which is known to regulate virus infectivity. Further, MeRIP-qPCR and mRNA stability analyses suggest that ALKBH5 regulates the expression of GAS6 via an m6A-YTHDF2-dependent mechanism. Overall, our study demonstrates that PEDV can infect porcine lung tissue and 3D4/21 cells and reveals the crucial role of ALKBH5 in restraining PEDV infections, at least partly, by influencing GAS6 through an m6A-YTHDF2-dependent mechanism.


Subject(s)
Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Macrophages, Alveolar , Porcine epidemic diarrhea virus/physiology , Swine , Swine Diseases/genetics , Virus Replication
3.
Sci Rep ; 12(1): 8145, 2022 May 17.
Article in English | MEDLINE | ID: covidwho-1864761

ABSTRACT

Wild boar (Sus scrofa L.) is one of the large mammals most spread worldwide, highly adaptable, and its population rapidly increased in many areas in Europe, including Italy, where Tuscany is considered particularly suitable for wild boar. Wild boars are potential hosts for different etiological agents, such as Brucella spp., Leptospira spp. and Pseudorabies virus and they can contribute to maintain and/or to disseminate some bacterial or viral pathogens to humans and domestic animals, above all-in free-range farms. In order to identify hypothetical genomic regions associated with these infection diseases, 96 samples of wild boars hunted in Tuscany during the 2018-2019 and 2019-2020 hunting seasons were considered. Diagnosis was achieved by serological tests and 42 Pseudorabies, 31 Leptospira and 15 Brucella positive animals were identified. All animals were genotyped with Geneseek Genomic Profiler Porcine HD (70 k) and a genome-wide scan was then performed. Significant markers were highlighted for Pseudorabies (two SNPs), Brucella (seven SNPs), and Leptospira (four SNPs) and they were located within, or nearby, 29 annotated genes on chromosome 6, 9, 12, 13, 14 and 18. Eight genes are implicated in viral (SEC14L1, JMJD6, SRSF2, TMPRSS2, MX1, MX2) or bacterial (COL8A1, SPIRE1) infections, seven genes (MFSD11, METTL23, CTTNBP2, BACE2, IMPA2, MPPE1 and GNAL) are involved in mental disorders and one gene (MGAT5B) is related to the Golgi complex. Results presented here provide interesting starting points for future research, validation studies and fine mapping of candidate genes involved in bacterial and viral infections in wild boar.


Subject(s)
Brucella , Leptospira , Pseudorabies , Swine Diseases , Virus Diseases , Animals , Carrier Proteins , Humans , Italy/epidemiology , Jumonji Domain-Containing Histone Demethylases , Leptospira/genetics , Phosphoprotein Phosphatases , Sus scrofa , Swine , Virus Diseases/epidemiology
4.
J Virol ; 96(11): e0046922, 2022 Jun 08.
Article in English | MEDLINE | ID: covidwho-1854236

ABSTRACT

Coronavirus (CoV) nonstructural protein 1 (nsp1) inhibits cellular gene expression and antagonizes interferon (IFN) response. Porcine epidemic diarrhea virus (PEDV) infects pigs and causes high mortality in neonatal piglets. We hypothesized that a recombinant PEDV carrying mutations at the conserved residues N93 and N95 of nsp1 induces higher IFN responses and is more sensitive to IFN responses, leading to virus attenuation. We mutated PEDV nsp1 N93 and N95 to A93 and A95 to generate the recombinant N93/95A virus using the infectious clone of a highly virulent PEDV strain, PC22A (icPC22A), and evaluated N93/95A virus in vitro and in vivo. Compared with icPC22A, the N93/95A mutant replicated to significantly lower infectious titers, triggered stronger type I and III IFN responses, and was more sensitive to IFN treatment in vitro. To evaluate the pathogenicity and immunogenicity, 5-day-old gnotobiotic piglets were orally inoculated with the N93/95A or icPC22A strain or mock inoculated and then challenged at 22 days postinoculation (dpi) with icPC22A. icPC22A in all pigs (100% [5/5]) caused severe diarrhea and death within 6 dpi. Only one pig (25% [1/4]) died in the N93/95A group. Compared with the icPC22A group, significantly delayed and diminished fecal PEDV shedding was detected in the N93/95A group. Postchallenge, all piglets in N93/95A group were protected from severe diarrhea and death, whereas all pigs in the mock-challenged group developed severe diarrhea, and 25% (1/4) of them died. In summary, nsp1 N93A and N95A mutations attenuated PEDV but retained viral immunogenicity and can be targets for the development of live attenuated vaccines for PEDV. IMPORTANCE PEDV causes porcine epidemic diarrhea (PED) and remains a great threat to the swine industry worldwide because no effective vaccines are available yet. Safe and effective live attenuated vaccines can be designed using reverse genetics to induce lactogenic immunity in pregnant sows to protect piglets from the deadly PED. We found that an engineered PEDV mutant carrying N93A and N95A mutations of nsp1 was partially attenuated and remained immunogenic in neonatal pigs. Our study suggested that nsp1 N93 and N95 can be good targets for the rational design of live attenuated vaccines for PEDV using reverse genetics. Because CoV nsp1 is conserved among alphacoronaviruses (α-CoVs) and betacoronaviruses (ß-CoVs), it may be a good target for vaccine development for other α-CoVs or ß-CoVs.


Subject(s)
Coronavirus Infections , Interferons , Porcine epidemic diarrhea virus , Swine Diseases , Viral Nonstructural Proteins , Animals , Animals, Newborn , Coronavirus Infections/immunology , Coronavirus Infections/veterinary , Diarrhea/veterinary , Diarrhea/virology , Female , Interferons/immunology , Mutation , Swine , Swine Diseases/immunology , Swine Diseases/virology , Viral Nonstructural Proteins/genetics
5.
Vet Q ; 42(1): 125-147, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1852679

ABSTRACT

Swine coronaviruses (SCoVs) are one of the most devastating pathogens affecting the livelihoods of farmers and swine industry across the world. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV). Coronaviruses infect a wide variety of animal species and humans because these are having single stranded-RNA that accounts for high mutation rates and thus could break the species barrier. The gastrointestinal, cardiovascular, and nervous systems are the primary organ systems affected by SCoVs. Infection is very common in piglets compared to adult swine causing high mortality in the former. Bat is implicated to be the origin of all CoVs affecting animals and humans. Since pig is the only domestic animal in which CoVs cause a wide range of diseases; new coronaviruses with high zoonotic potential could likely emerge in the future as observed in the past. The recently emerged severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), causing COVID-19 pandemic in humans, has been implicated to have animal origin, also reported from few animal species, though its zoonotic concerns are still under investigation. This review discusses SCoVs and their epidemiology, virology, evolution, pathology, wildlife reservoirs, interspecies transmission, spill-over events and highlighting their emerging threats to swine population. The role of pigs amid ongoing SARS-CoV-2 pandemic will also be discussed. A thorough investigation should be conducted to rule out zoonotic potential of SCoVs and to design appropriate strategies for their prevention and control.


Subject(s)
COVID-19 , Porcine epidemic diarrhea virus , Swine Diseases , Alphacoronavirus , Animals , COVID-19/epidemiology , COVID-19/veterinary , Humans , Pandemics , SARS-CoV-2 , Swine , Swine Diseases/epidemiology
6.
Vet Microbiol ; 269: 109448, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1829627

ABSTRACT

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a typical neurotropic betacoronavirus causing digestive disease and/or neurological dysfunction in neonatal pigs. Actin filaments have been identified to implicate in PHEV invasion, but the effects of viral infection on microtubules (MTs) cytoskeleton are unknown. Here, we observed that PHEV infection induced MT depolymerization and was accompanied by the disappearance of microtubule organizing centers. Depolymerization of MTs induced by nocodazole significantly inhibited viral RNA replication, but over-polymerization of MTs induced by paclitaxel did not substantially affect PHEV infection. The expression of histone deacetylase 6 (HDAC6), an important regulator of MT acetylation, progressively increased during PHEV infection. Tramstatin A could alter HDAC6 deacetylase activity to enhance the acetylation of the substrate α-tubulin and MT polymerization, but does not increase PHEV proliferation. These findings suggest that PHEV could subvert host MT cytoskeleton to facilitate infection, and that MT depolymerization negatively affects viral replication independently of HDAC6 activity.


Subject(s)
Betacoronavirus 1 , Coronavirus Infections , Swine Diseases , Animals , Betacoronavirus , Coronavirus Infections/veterinary , Microtubules , Swine , Tubulin/genetics , Tubulin/metabolism , Virus Replication
7.
Proc Natl Acad Sci U S A ; 119(18): e2118126119, 2022 05 03.
Article in English | MEDLINE | ID: covidwho-1815697

ABSTRACT

Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV.


Subject(s)
Alphacoronavirus , Coronavirus Infections , Swine Diseases , Alphacoronavirus/genetics , Animals , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Coronavirus Infections/epidemiology , Swine
8.
Viruses ; 14(4)2022 04 08.
Article in English | MEDLINE | ID: covidwho-1810315

ABSTRACT

Porcine deltacoronavirus (PDCoV) mainly causes severe diarrhea and intestinal pathological damage in piglets and poses a serious threat to pig farms. Currently, no effective reagents or vaccines are available to control PDCoV infection. Single-chain fragment variable (scFv) antibodies can effectively inhibit virus infection and may be a potential therapeutic reagent for PDCoV treatment. In this study, a porcine phage display antibody library from the peripheral blood lymphocytes of piglets infected with PDCoV was constructed and used to select PDCoV-specific scFv. The library was screened with four rounds of biopanning using the PDCoV N protein, and the colony with the highest affinity to the PDCoV N protein was obtained (namely, N53). Then, the N53-scFv gene fragment was cloned into plasmid pFUSE-hIgG-Fc2 and expressed in HEK-293T cells. The scFv-Fc antibody N53 (namely, scFv N53) was purified using Protein A-sepharose. The reactive activity of the purified antibody with the PDCoV N protein was confirmed by indirect enzyme-linked immunosorbent assay (ELISA), western blot and indirect immunofluorescence assay (IFA). Finally, the antigenic epitopes that the scFv N53 recognized were identified by a series of truncated PDCoV N proteins. The amino acid residues 82GELPPNDTPATTRVT96 of the PDCoV N protein were verified as the minimal epitope that can be recognized by the scFv-Fc antibody N53. In addition, the interaction between the scFv-Fc antibody N53 and the PDCoV N protein was further analyzed by molecule docking. In conclusion, our research provides some references for the treatment and prevention of PDCoV.


Subject(s)
Bacteriophages , Coronavirus Infections , Single-Chain Antibodies , Swine Diseases , Animals , Antibodies, Viral , Deltacoronavirus , Epitopes , Nucleocapsid Proteins/genetics , Single-Chain Antibodies/genetics , Swine , Technology
9.
Vet Microbiol ; 270: 109447, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1805301

ABSTRACT

Enteric disease is the predominant cause of morbidity and mortality in young mammals including pigs. Viral species involved in porcine enteric disease complex (PEDC) include rotaviruses, coronaviruses, picornaviruses, astroviruses and pestiviruses among others. The virome of three groups of swine samples submitted to the Kansas State University Veterinary Diagnostic Laboratory for routine testing were assessed, namely, a Rotavirus A positive (RVA) group, a Rotavirus co-infection (RV) group and a Rotavirus Negative (RV Neg) group. All groups were designated by qRT-PCR test results for Porcine Rotavirus A, B, C and H such that samples positive for RVA only went in the RVA group, samples positive for > 1 rotavirus went in the RV group and samples negative for all were grouped in the RVNeg group. All of the animals had clinical enteric disease resulting in scours and swollen joints/lameness, enlarged heart and/or a cough. All samples were metagenomic sequenced and analyzed for viral species composition that identified 14 viral species and eight bacterial viruses/phages. Sapovirus and Escherichia coli phages were found at a high prevalence in RVA and RV samples but were found at low or no prevalence in the RVNeg samples. Picobirnavirus was identified at a high proportion and prevalence in RVNeg and RV samples but at a low prevalence in the RVA group. Non-rotaviral diversity was highest in RVA samples followed by RV then RV Neg samples. A sequence analysis of the possible host of Picobirnaviruses revealed fungi as the most likely host. Various sequences were extracted from the sample reads and a phylogenetic update was provided showing a high prevalence of G9 and P[23] RVA genotypes. These data are important for pathogen surveillance and control measures.


Subject(s)
Rotavirus Infections , Rotavirus , Swine Diseases , Animals , Diarrhea/epidemiology , Diarrhea/veterinary , Feces , Genotype , Humans , Mammals , Phylogeny , Rotavirus/genetics , Rotavirus Infections/epidemiology , Rotavirus Infections/veterinary , Swine , Swine Diseases/epidemiology , Virome
10.
J Virol ; 96(9): e0038022, 2022 05 11.
Article in English | MEDLINE | ID: covidwho-1794532

ABSTRACT

Crossing the endothelium from the entry site and spreading in the bloodstream are crucial but obscure steps in the pathogenesis of many emerging viruses. Previous studies confirmed that porcine epidemic diarrhea virus (PEDV) caused intestinal infection by intranasal inoculation. However, the role of the nasal endothelial barrier in PEDV translocation remains unclear. Here, we demonstrated that PEDV infection causes nasal endothelial dysfunction to favor viral dissemination. Intranasal inoculation with PEDV compromised the integrity of endothelial cells (ECs) in nasal microvessels. The matrix metalloproteinase 7 (MMP-7) released from the PEDV-infected nasal epithelial cells (NECs) contributed to the destruction of endothelial integrity by degrading the tight junctions, rather than direct PEDV infection. Moreover, the proinflammatory cytokines released from PEDV-infected NECs activated ECs to upregulate ICAM-1 expression, which favored peripheral blood mononuclear cells (PBMCs) migration. PEDV could further exploit migrated cells to favor viral dissemination. Together, our results reveal the mechanism by which PEDV manipulates the endothelial dysfunction to favor viral dissemination and provide novel insights into how coronavirus interacts with the endothelium. IMPORTANCE The endothelial barrier is the last but vital defense against systemic viral transmission. Porcine epidemic diarrhea virus (PEDV) can cause severe atrophic enteritis and acute viremia. However, the mechanisms by which the virus crosses the endothelial barrier and causes viremia are poorly understood. In this study, we revealed the mechanisms of endothelial dysfunction in PEDV infection. The viral infection activates NECs and causes the upregulation of MMP-7 and proinflammatory cytokines. Using NECs, ECs, and PBMCs as in vitro models, we determined that the released MMP-7 contributed to the destruction of endothelial barrier, and the released proinflammatory cytokines activated ECs to facilitate PBMCs migration. Moreover, the virus further exploited the migrated cells to promote viral dissemination. Thus, our results provide new insights into the mechanisms underlying endothelial dysfunction induced by coronavirus infection.


Subject(s)
Coronavirus Infections , Endothelium , Porcine epidemic diarrhea virus , Swine Diseases , Virus Shedding , Animals , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cytokines , Endothelium/virology , Intercellular Adhesion Molecule-1/genetics , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/virology , Matrix Metalloproteinase 7/metabolism , Porcine epidemic diarrhea virus/physiology , Swine , Swine Diseases/immunology , Swine Diseases/transmission , Swine Diseases/virology , Viremia
11.
Viruses ; 14(4)2022 04 17.
Article in English | MEDLINE | ID: covidwho-1792412

ABSTRACT

Porcine enteric coronaviruses have caused immense economic losses to the global pig industry, and pose a potential risk for cross-species transmission. The clinical symptoms of the porcine enteric coronaviruses (CoVs) are similar, making it difficult to distinguish between the specific pathogens by symptoms alone. Here, a multiplex nucleic acid detection platform based on CRISPR/Cas12a and multiplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) was developed for the detection of four diarrhea CoVs: porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). With this strategy, we realized a visual colorimetric readout visible to the naked eye without specialized instrumentation by using a ROX-labeled single-stranded DNA-fluorescence-quenched (ssDNA-FQ) reporter. Our method achieved single-copy sensitivity with no cross-reactivity in the identification and detection of the target viruses. In addition, we successfully detected these four enteric CoVs from RNA of clinical samples. Thus, we established a rapid, sensitive, and on-site multiplex molecular differential diagnosis technology for porcine enteric CoVs.


Subject(s)
Coronavirus Infections , Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Alphacoronavirus , Animals , CRISPR-Cas Systems , Coronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/genetics , Coronavirus Infections/veterinary , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Porcine epidemic diarrhea virus/genetics , RNA-Directed DNA Polymerase/genetics , Sensitivity and Specificity , Swine
12.
Arch Virol ; 167(5): 1381-1385, 2022 May.
Article in English | MEDLINE | ID: covidwho-1782822

ABSTRACT

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a member of the subgenus Embecovirus of the genus Betacoronavirus, and it is ubiquitously distributed in most pig-farming countries worldwide with low clinical incidence. Here, we report the full-length genome sequence and molecular characterization of a novel PHEV strain identified in diarrheic neonates in South Korea. The complete genome of the Korean PHEV strain GNU-2113 was sequenced and analyzed to characterize PHEV circulating in South Korea. The GNU-2113 genome was determined to be 29,982 nucleotides in length, with large unique deletions in the regions encoding nonstructural protein 3 and NS2. It was found to share 95.1-96.9% sequence identity with other global strains. Genetic and phylogenetic analysis indicated that the GNU-2113 strain is distantly related to the existing PHEV genotypes, implying that the virus appears to undergo substantial evolution under endemic pressure. This study provides important information about the genetic diversity of PHEV circulating subclinically in swine herds, which may ensure viral fitness in the enzootic environment.


Subject(s)
Betacoronavirus 1 , Swine Diseases , Animals , Betacoronavirus 1/genetics , Genome, Viral , Genotype , Phylogeny , Republic of Korea , Sequence Analysis, DNA , Swine
13.
Int J Mol Sci ; 23(7)2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1785740

ABSTRACT

Swine enteric coronavirus (SeCoV) causes acute gastroenteritis and high mortality in newborn piglets. Since the last century, porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) have swept farms all over the world and caused substantial economic losses. In recent years, porcine delta coronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) have been emerging SeCoVs. Some of them even spread across species, which made the epidemic situation of SeCoV more complex and changeable. Recent studies have begun to reveal the complex SeCoV-host interaction mechanism in detail. This review summarizes the current advances in autophagy, apoptosis, and innate immunity induced by SeCoV infection. These complex interactions may be directly involved in viral replication or the alteration of some signal pathways.


Subject(s)
Coronavirus Infections , Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Alphacoronavirus , Animals , Host-Pathogen Interactions , Swine
14.
Front Public Health ; 10: 836177, 2022.
Article in English | MEDLINE | ID: covidwho-1776039

ABSTRACT

Taenia solium cysticercosis is the most common cause of acquired epilepsy in pig-raising and pork-consuming parts of Africa, Latin America, and Asia. This review aimed to systematically compile and synthesize data on the epidemiology of porcine cysticercosis in the Eastern and Southern Africa (ESA) region. Comprehensive searching strategies were employed to retrieve the studies published or reported between January 1,1997 and March 1, 2021, from Pub Med, Hinari, and Google Scholar databases and search platforms. The identified studies that met the inclusion criteria were then appraised for methodological quality. Finally, 44 studies obtained from nine countries were selected and included in this review. Relevant data were extracted using standardized templates for qualitative synthesis and meta-analysis. The overall pooled prevalence estimate of porcine cysticercosis in the ESA region was 17% (95% CI: 14-20%). The prevalence level between and within countries showed high variability. The pooled estimate showed high heterogeneity among the reports (the inverse variance index value (I2) of 98.99%, p < 0.05). The meta-analysis sub-grouped by the type of diagnostic test showed the pooled prevalence estimate of 27% (95% CI: 9-50) by carcass dissection; 23% (95% CI: 14-33) by Antibody-based immunodiagnostic techniques; 23% (95% CI: 18-29) by antigen detecting (Ag)-ELISA, 12% (95% CI: 7-18) by meat inspection, and 9% (95% CI: 7-11) by lingual examination. The meta-analysis sub-grouped by region showed a relatively higher pooled prevalence estimate for the Southern region 22% (95% CI: 15-30) compared to 13% (95% CI: 11-15) in the Eastern region. The highest country-based pooled prevalence was obtained from South Africa (33%, 95% CI: 20-48) and Zambia (22%, 95% CI: 16-29), whereas the lowest pooled prevalence was identified in Madagascar (5%, 95% CI: 4-5) and Rwanda (7%, 95% CI: 6-8). The lack of latrine, traditional pig husbandry practices, unprotected water sources, and increase in age were identified as significant risk factors for the occurrence of porcine cysticercosis in the pooled studies. The findings of this review will provide context-specific input to prioritize the possible intervention programs for T. solium control in the ESA region. More sensitive and specific test-based prevalence estimates, detailed risk factor investigations, and financial losses analysis are needed to establish feasible control strategies. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021238931.


Subject(s)
Cysticercosis , Swine Diseases , Africa, Southern , Animals , Cysticercosis/epidemiology , Cysticercosis/veterinary , Enzyme-Linked Immunosorbent Assay , Swine , Swine Diseases/epidemiology
15.
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
16.
BMC Vet Res ; 18(1): 124, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1770541

ABSTRACT

BACKGROUND: Coronaviruses have the potential to cross species barriers. To learn the molecular intersections among the most common coronaviruses of domestic and close-contact animals, we analyzed representative coronavirus genera infecting mouse, rat, rabbit, dog, cat, cattle, white-tailed deer, swine, ferret, mink, alpaca, Rhinolophus bat, dolphin, whale, chicken, duck and turkey hosts; reference or complete genome sequences were available for most of these coronavirus genera. Protein sequence alignments and phylogenetic trees were built for the spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The host receptors and enzymes aminopeptidase N (APN), angiotensin converting enzyme 2 (ACE2), sialic acid synthase (SAS), transmembrane serine protease 2 (TMPRSS2), dipeptidyl peptidase 4 (DPP4), cathepsin L (and its analogs) and furin were also compared. RESULTS: Overall, the S, E, M, and N proteins segregated according to their viral genera (α, ß, or γ), but the S proteins of alphacoronaviruses lacked conservation of phylogeny. Interestingly, the unique polybasic furin cleavage motif found in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) but not in severe acute respiratory syndrome coronavirus (SARS-CoV) or Middle East respiratory syndrome coronavirus (MERS-CoV) exists in several ß-coronaviruses and a few α- or γ-coronaviruses. Receptors and enzymes retained host species-dependent relationships with one another. Among the hosts, critical ACE2 residues essential for SARS-CoV-2 spike protein binding were most conserved in white-tailed deer and cattle. CONCLUSION: The polybasic furin cleavage motif found in several ß- and other coronaviruses of animals points to the existence of an intermediate host for SARS-CoV-2, and it also offers a counternarrative to the theory of a laboratory-engineered virus. Generally, the S proteins of coronaviruses show crossovers of phylogenies indicative of recombination events. Additionally, the consistency in the segregation of viral proteins of the MERS-like coronavirus (NC_034440.1) from pipistrelle bat supports its classification as a ß-coronavirus. Finally, similarities in host enzymes and receptors did not always explain natural cross-infections. More studies are therefore needed to identify factors that determine the cross-species infectivity of coronaviruses.


Subject(s)
COVID-19 , Cattle Diseases , Deer , Dog Diseases , Middle East Respiratory Syndrome Coronavirus , Rodent Diseases , Swine Diseases , Animals , COVID-19/veterinary , Cattle , Dogs , Ferrets , Mice , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Rabbits , Rats , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Swine
17.
Viruses ; 14(3)2022 02 27.
Article in English | MEDLINE | ID: covidwho-1765944

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is the major pathogen that causes diarrhea and high mortality in newborn piglets, with devastating impact on the pig industry. To further understand the molecular epidemiology and genetic diversity of PEDV field strains, in this study the complete genomes of four PEDV variants (HN2021, CH-HNYY-2018, CH-SXWS-2018, and CH-HNKF-2016) obtained from immunized pig farms in central China between 2016 to 2021 were characterized and analyzed. Phylogenetic analysis of the genome and S gene showed that the four strains identified in the present study had evolved into the subgroup G2a, but were distant from the vaccine strain CV777. Additionally, it was noteworthy that a new PEDV strain (named HN2021) belonging to the G2a PEDV subgroup was successfully isolated in vitro and it was further confirmed by RT-PCR that this isolate had a large natural deletion at 207-373 nt of the ORF3 gene, which has never been reported before. Particularly, in terms of pathogenicity evaluation, colostrum deprivation piglets challenged with PEDV HN2021 showed severe diarrhea and high mortality, confirming that PEDV HN2021 was a virulent strain. Hence, PEDV strain HN2021 of subgroup G2a presents a promising vaccine candidate for the control of recurring porcine epidemic diarrhea (PED) in China. This study lays the foundation for better understanding of the genetic evolution and molecular pathogenesis of PEDV.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Vaccines , Animals , China/epidemiology , Diarrhea , Phylogeny , Swine , Virulence
18.
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
19.
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
20.
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
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