Veterinary Research最新文献

{"title":"Transferrin knockout reveals a tolerance phenotype against Piscirickettsia salmonis in Atlantic salmon phagocytes.","authors":"Madelaine Mejías, Alejandro Sáez, Amanda Escorza, Felipe Galdames-Contreras, Yehwa Jin, Phillip Dettleff, Ingrid Ojeda, Rodrigo Pulgar, Sebastián Escobar-Aguirre","doi":"10.1186/s13567-025-01607-8","DOIUrl":"10.1186/s13567-025-01607-8","url":null,"abstract":"<p><p>Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, is a major challenge in Chilean aquaculture. We evaluated the impact of the vaccine on fish survival, bacterial load, and iron metabolism-related gene expression under field conditions. Atlantic salmon received either a pentavalent inactivated vaccine plus a live attenuated P. salmonis vaccine (SIA) or a tetravalent control vaccine (SS). While survival was similar early (≤ 28 weeks post-seawater transfer), SIA-vaccinated fish showed greater survival by week 41 (85% vs. 52%). Quantitative PCR confirmed a reduced bacterial load in the SIA group during active infection. Expression analysis revealed distinct temporal regulation of iron metabolism genes: ferritin and hepcidin were upregulated in freshwater, whereas transferrin and its receptor were elevated in seawater in the SIA group, suggesting a link between iron homeostasis and vaccine-induced protection. To further investigate the role of transferrin, we generated transferrin-knockout (TF-KO) phagocytes using CRISPR/Cas9. In vitro infection assays revealed that, compared with wild-type (TF-WT) cells, TF-KO cells presented reduced cytopathic effects, decreased formation of P. salmonis-containing vacuoles (PCVs), and improved viability. Surprisingly, no differences in bacterial load or iron-related gene expression were detected between TF-KO and TF-WT cells, indicating that transferrin disruption did not directly alter iron homeostasis. Global transcriptomic analysis revealed 311 differentially expressed genes in TF-KO cells, with functional enrichment in metal-binding and zinc-dependent processes but no direct association with iron metabolism. These findings suggest that transferrin deficiency confers an infection-tolerant phenotype through transcriptional reprogramming unrelated to iron regulation, highlighting novel mechanisms of host‒pathogen interactions and potential avenues for SRS control in aquaculture.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"180"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cav1.2 facilitates the binding and internalisation of porcine epidemic diarrhoea virus.","authors":"Xinxin Wang, Guilan Guo, Shutong He, Kaili Wang, Jianing Chen, Guijie Guo","doi":"10.1186/s13567-025-01615-8","DOIUrl":"10.1186/s13567-025-01615-8","url":null,"abstract":"<p><p>Porcine epidemic diarrhoea virus (PEDV) has caused substantial economic losses to the global swine industry. The PEDV spike (S) protein mediates viral entry by interacting with host receptors. However, the molecular mechanisms underlying PEDV entry remain incompletely understood. In this study, we identified the L-type calcium channel Cav1.2 as a critical host factor for PEDV entry. Depletion of Cav1.2 significantly suppressed PEDV replication. Additionally, treatment with the FDA-approved Cav1.2 blocker diltiazem inhibited PEDV replication and disrupted early infection events. Mechanistically, we found that Cav1.2 interacts with the PEDV S1 subunit. Both Cav1.2 knockdown and diltiazem treatment substantially reduced the binding and internalisation of PEDV. These findings reveal that Cav1.2 is a key host factor for PEDV binding and internalisation via interaction with the viral S protein, and suggest that Cav1.2 may serve as a promising target for antiviral drug development against PEDV.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"183"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper-mediated MAM regulation of the NF-κB signalling pathway enhances Seneca Valley virus replication in PK-15 cells.","authors":"Xiaoli Wu, Song Zhu, Min Li, Zhiwen Xu, Ling Zhu, Junliang Deng, Huidan Deng","doi":"10.1186/s13567-025-01578-w","DOIUrl":"10.1186/s13567-025-01578-w","url":null,"abstract":"<p><p>Seneca Valley virus (SVV) is known to cause vesicular disease in swine, presenting new challenges to the pig industry. Recent studies have investigated the relationship between disrupted copper ion homeostasis and viral replication, suggesting that copper dysregulation has a significant impact on the replication of various viruses. Research has also shown that mitochondria-associated endoplasmic reticulum membrane (MAM) and NF-κB are involved in the innate immune response triggered by viral infections. However, the exact mechanisms by which copper (Cu), MAM, and NF-κB affect SVV replication remain unclear. In this study, it was found that SVV induces an imbalance in copper homeostasis, leading to dynamic changes in MAM while inhibiting the NF-κB pathway. This inhibition results in decreased levels of IL-6, IL-1β, TNF-α, IFN-α, and IFNλ3. Furthermore, the disruption of copper homeostasis in SVV-infected PK-15 cells regulates the NF-κB pathway through MAM, promoting SVV replication. This research provides valuable insights into the regulation of copper metabolism during SVV infection and establishes a theoretical framework for understanding the pathogenesis and immune activation mechanisms associated with SVV.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"175"},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of recombinant bovine β-defensins for antimicrobial and anti-inflammatory functions in sepsis management.","authors":"Cristina Saubi, Ricardo Baltà-Foix, Jose Vicente Carratalá, Francesc Fàbregas, Daniel Sandín, Marc Torrent, Elena Garcia-Fruitós, Anna Arís","doi":"10.1186/s13567-025-01601-0","DOIUrl":"10.1186/s13567-025-01601-0","url":null,"abstract":"<p><p>β-defensins are multifunctional peptides of the host immune system involved in responses to infectious diseases. We investigated the potential of five recombinant proteins based on bovine β-defensins (bovine neutrophil β-defensins (BNBD) 1, 2, 3, and 4, and the tracheal antimicrobial peptide (TAP)) in functions relevant to sepsis such as antimicrobial activity, lipopolysaccharide (LPS) binding and neutralisation, and the stimulation of cytokine response in epithelial cells. These β-defensins were produced in Lactococcus lactis as fusion proteins. Antimicrobial activity was tested against Escherichia coli; LPS binding and neutralisation were assessed using a fluorescent probe displacement assay and by measuring tumour necrosis factor alpha (TNFα) levels in whole blood after an LPS challenge, respectively. Interleukin-8 (IL-8) levels were quantified to evaluate the epithelial immune response. All β-defensins exhibited different properties, suggesting they may have distinct mechanisms and functions in resolving infections. The recombinant BNBD4 showed potent antimicrobial activity against E. coli, whereas TAP was more notable for its ability to bind and neutralise LPS. These findings suggest that β-defensins, particularly BNBD4 and TAP, may be utilised to treat sepsis by targeting bacterial pathogens and modulating inflammatory responses.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"173"},"PeriodicalIF":3.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of an enterococcal phage endolysin as a potential antimicrobial agent against Streptococcus suis.","authors":"Jing Wang, Yaowei Liu, Siyu Liang, Xiaofeng Lu, Qiu Xu, Cuilong Fan, Wanjiang Zhang, Siguo Liu, Fang Xie","doi":"10.1186/s13567-025-01608-7","DOIUrl":"10.1186/s13567-025-01608-7","url":null,"abstract":"<p><p>Streptococcus suis, an important zoonotic pathogen capable of transmission from pigs to humans, represents a critical threat to both public health and the global pork industry. The increasing prevalence of multidrug-resistant S. suis strains, coupled with their ability to form biofilms, has necessitated the development of alternative antimicrobial strategies. In this study, we characterized the therapeutic potential of Ply113, an endolysin derived from an Enterococcus faecium phage, against S. suis. Ply113 has shown potent bactericidal activity against S. suis in vitro, with rapid time-kill characteristics and broad-spectrum efficiency against clinically prevalent serotypes (2, 3, 4, 7, and 9). Transmission electron microscopy analysis revealed that Ply113 induced distinct morphological alterations in S. suis, including cell wall disintegration and cytoplasmic leakage. This endolysin exhibited anti-biofilm functionality, eradicating biofilms formed by clinical strain of S. suis in a concentration-dependent manner. In murine models of bacteremia, a single administration of Ply113 provided complete protection against lethal S. suis infection, significantly decreasing the bacterial burden in the liver and spleen and attenuating organ injury. Additionally, Ply113 has been shown to be safe for mice, with no adverse effects. Taken together, our findings indicate that Ply113 is a promising alternative antimicrobial agent for combating biofilm-related infections caused by S. suis.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"174"},"PeriodicalIF":3.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-glycosylation of the PEDV spike protein modulates viral replication and pathogenicity.","authors":"Huixin Zhu, Zhaoyang Feng, Meng Sun, Sinuo Zhang, Zhen Yang, Juan Bai, Ping Jiang, Gongguan Liu, Xing Liu, Xianwei Wang","doi":"10.1186/s13567-025-01606-9","DOIUrl":"https://doi.org/10.1186/s13567-025-01606-9","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV), a highly virulent enteric coronavirus, induces severe watery diarrhea and mortality in suckling piglets. The spike (S) protein, a critical mediator of viral entry, undergoes extensive N-linked glycosylation. To elucidate the functional significance of these post-translational modifications, we employed a reverse genetics system to generate 19 recombinant PEDV strains with single-site mutations at predicted N-glycosylation sites. In vitro experiments revealed that mutations at residues N118, N216, N726, N1232, and N1249 significantly attenuated viral replication and reduced plaque size. Our data demonstrated that these mutations impaired viral attachment and internalization. Importantly, in vivo pathogenicity assays in piglets indicated that the N1232Q and N1249Q mutants presented minimal faecal viral shedding and no clinical symptoms, suggesting their potential as live attenuated vaccine candidates. These findings underscore the critical role of S protein glycosylation in PEDV infectivity and virulence, providing a molecular basis for rational vaccine design.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"172"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxoplasma gondii PPM3H regulates the parasite virulence and modulates host immune and inflammatory responses in mice.","authors":"Jun-Jun He, Jun Ma, Meng-Ling Deng, Hany M Elsheikha, Yi-Dan Wang, Yu-Cong Zhang, Feng-Cai Zou, Xing-Quan Zhu","doi":"10.1186/s13567-025-01603-y","DOIUrl":"https://doi.org/10.1186/s13567-025-01603-y","url":null,"abstract":"<p><p>Toxoplasma gondii is an obligate intracellular parasite that causes severe illness in infants infected during pregnancy and in immunocompromised individuals. This parasite manipulates host cells through effector proteins that promote its survival and replication. While the phosphatases in the PP2C family have been shown to regulate host immune responses and contribute to the virulence and pathogenicity of various pathogens, the specific biological functions of PPM3H in T. gondii and its role in host-pathogen interactions remain unclear. In this study, we demonstrate that knockout of ppm3h significantly reduces the virulence and pathogenicity of T. gondii. In contrast, that high expression of ppm3h in the less virulent PRU induced by replacing the ppm3h gene elements of RH strain can enhance its pathogenicity, indicating a direct contribution of PPM3H to virulence in expression-independent manner. Furthermore, PPM3H significantly influenced host gene expression, with differentially expressed genes predominantly enriched in immune and inflammatory pathways. Weighted gene co-expression network analysis identified host immune genes, including chemokines such as Cx3cl1 and Ccl22, as co-expressed with ppm3h. Also, ppm3h co-expressed with T. gondii rhoptry genes including rop18, a well-known virulence factor, suggesting a role for PPM3H in coordinating host-pathogen interactions. Our findings establish that PPM3H enhances T. gondii virulence by modulating the host immune and inflammatory responses. PPM3H does not impact parasite gene expression, invasion or replication in vitro, supporting its role as an immune modulator rather than a general fitness factor. This suggests that T. gondii's pathogenicity arises not only from immune evasion but also from the active induction of host immune and inflammatory responses mediated by PPM3H.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"171"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beware of host immune responses towards bacteriophages potentially impacting phage therapy.","authors":"Thomas Démoulins, Jérémy D R Cherbuin, Thatcha Yimthin, Lukas Eggerschwiler, Fazal Adnan, Joerg Jores","doi":"10.1186/s13567-025-01600-1","DOIUrl":"10.1186/s13567-025-01600-1","url":null,"abstract":"<p><p>The rising spread of antimicrobial resistance challenges animal welfare, productivity and food supply with respect to bacterial infections in different livestock species. Bacteriophages offer alternative means to control infections with resistant bacteria. This work investigated the host immune responses towards lytic bacteriophages K and T1, acting respectively on Gram-positive or Gram-negative bacteria. We employed an ex vivo platform to decipher various immune responses elicited by primary blood cells of eight outbred cattle. Bacteriophage K was not recognized whereas bacteriophage T1 induced a profound immune response. Therefore, prior characterization of host immune responses towards therapeutic phages should be considered before therapy starts.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"170"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of monoclonal antibodies specific for bovine IP-10.","authors":"Hamza Khalid, Michael Coad, Inga Dry, Catherine McGuinnes, Lindsey A Waddell, Jayne C Hope, Zhiguang Wu","doi":"10.1186/s13567-025-01602-z","DOIUrl":"10.1186/s13567-025-01602-z","url":null,"abstract":"<p><p>Research on chemokines in cattle is hampered by the relative lack of validated reagents. Bovine IP-10 is an important inflammatory chemokine and a promising diagnostic biomarker for an economically important disease (bovine tuberculosis) caused by infection of cattle with Mycobacterium bovis. Currently no monoclonal antibodies are available for bovine IP-10. The goal of this study was to generate novel mAbs for detection of bovine IP-10 using hybridoma technology. Five mAbs were developed and cross clone inhibition analyses showed a high degree of self-inhibition among the mAbs. One mAb (7C2) was used in conjugation with a commercial polyclonal antibody to develop a sandwich ELISA. Upon testing with recombinant bovine IP-10, this ELISA showed an enhanced linear range compared to the currently available polyclonal antibody-based ELISA. The ELISA using 7C2 was shown to detect native antigen-specific bovine IP-10 in samples from M. bovis infected animals. The 7C2 mAb could also detect intracytoplasmic IP-10. These novel mAbs will be useful in elucidating roles for IP-10 in bovine immune studies in health, disease and vaccination contexts.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"169"},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEDV infection downregulates goblet cell differentiation through activating the Notch pathway.","authors":"Yi Wang, Shanshan Yang, Yongxiang Zhao, Shuo Tian, Qiuxia Cao, Xinmei Geng, Mengdi Yang, Xu Song, Hongqi Shang, Shiyu Liu, Rongli Guo, Yunchuan Li, Min Sun, Mi Hu, Baochao Fan, Bin Li","doi":"10.1186/s13567-025-01599-5","DOIUrl":"10.1186/s13567-025-01599-5","url":null,"abstract":"<p><p>Porcine epidemic diarrhoea virus (PEDV) is the most widespread porcine coronavirus worldwide, causing high mortality and a high incidence rate among piglets. The molecular mechanisms by which PEDV regulates epithelial cell function and differentiation, as well as its disruption of the intestinal mucosal barrier, are not yet fully understood. This study reveals that PEDV infection reduces the number of goblet cells and impairs the intestinal barrier integrity in newborn piglets. Regarding the pathways involved in the differentiation of intestinal stem cells (ISCs), PEDV infection concurrently activates the Notch and MAPK pathways while suppressing the Wnt/β-catenin pathway in the intestines of piglets. Furthermore, in vitro experiments using intestinal monolayer organoid models showed that PEDV infection hinders goblet cell differentiation by activating the Notch signalling pathway. Additionally, the PEDV-encoded ORF3 protein, which is crucial for activating the Notch pathway, inhibits goblet cell differentiation in PEDV-infected intestinal monolayer organoids. This study offers new insights into the mechanisms underlying intestinal mucosal barrier dysfunction induced by PEDV infection.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"168"},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}