{"title":"Recent advancements in the diverse roles of polymerase-associated proteins in the replication and pathogenesis of Newcastle disease virus.","authors":"Jinghang Zhou, Yuqi Duan, Menglan Liu, Jinyang Liu, Zenglei Hu, Zhiqiang Duan","doi":"10.1186/s13567-024-01429-0","DOIUrl":"10.1186/s13567-024-01429-0","url":null,"abstract":"<p><p>Newcastle disease virus (NDV) is a significant member of the Paramyxoviridae family, known for causing epidemics and substantial economic losses in the poultry industry worldwide. The NDV RNA genome primarily encodes six structural proteins (N, P, M, F, HN, and L) and two non-structural proteins (V and W). Among these, the polymerase-associated proteins (N, P, and L) and the viral RNA (vRNA) genome form the ribonucleoprotein complex, which plays a crucial role in the synthesis and transcription of NDV vRNA. In the last two decades, numerous studies have demonstrated that the polymerase-associated proteins are linked to the virulence, pathotype, and thermostability of NDV. Additionally, the interactions between these polymerase-associated proteins and host proteins are closely related to the NDV's replication and pathogenicity. Despite significant progress in understanding the unique and shared functions of NDV polymerase-associated proteins, research on these viral proteins' structure and function is less comprehensive than other NDV proteins, and the available information is often scattered. Therefore, this article systematically summarises and reviews the research progress made in understanding the structural features, virulence, pathotype, and thermostability correlation of NDV polymerase-associated proteins, as well as the critical roles of interactions between polymerase-associated proteins and host proteins in NDV replication and pathogenicity. This review aims to enhance our understanding of the complex functions of polymerase-associated proteins in NDV replication and pathogenesis and to contribute to the development of more effective vaccines and antiviral drugs against NDV challenges.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"8"},"PeriodicalIF":3.7,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972340","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":"Effects of Trichinella spiralis and its serine protease inhibitors on intestinal mucosal barrier function.","authors":"Ruibiao Wang, Yuheng Zhang, Zhixin Li, Jingbo Zhen, Qiankun Li, Qi Zhang, Yuqi Yang, Xueting Liu, Yixin Lu","doi":"10.1186/s13567-024-01446-z","DOIUrl":"10.1186/s13567-024-01446-z","url":null,"abstract":"<p><p>Trichinella spiralis (T. spiralis) is a highly pathogenic zoonotic nematode that poses significant public health risks and causes substantial economic losses. Understanding its invasion mechanisms is crucial. This study explored how the serine protease inhibitors (SPIs) secreted by T. spiralis affect the host's intestinal epithelial barrier. Furthermore, the effects of T. spiralis infection on the jejunal barrier function in mice were investigated. The histopathological analysis indicated significant damage to the jejunum, which peaked at day 7 post-infection (dpi). The results of RT-qPCR and western blotting revealed marked reductions in tight junction proteins (ZO-1, occludin, claudin-3), mucins (MUC-1, MUC-2), and anti-inflammatory cytokines (TGF-β, IL-10) from 1 to 15 dpi. There was also increased expression of Toll-like receptors (TLR-1, TLR-2, TLR-4) and pro-inflammatory cytokines (TNF-α, IL-1β). Recombinant SPIs (rKaSPI, rAdSPI) were purified, co-cultured with intestinal epithelial cells (IPECs), and used in mouse models. The protein expression changes in IPECs and mice were consistent with those in T. spiralis-infected tissues. Both SPIs caused the down-regulation of ZO-1, occludin, claudin-3, MUC-1, MUC-2, TGF-β, and IL-10 while up-regulating TLR-4 and pro-inflammatory cytokines. As a result, the intestinal barrier was disrupted, and inflammation was exacerbated. Notably, rAdSPI had a more pronounced effect. In summary, T. spiralis infection caused significant jejunal damage and disrupted the intestinal barrier. T. spiralis-secreted SPIs, especially serpin-type serine protease inhibitors (AdSPI), were pivotal in facilitating invasion by compromising the host's intestinal barrier and promoting inflammation. This study provides insights into T. spiralis invasion mechanisms and the potential targets for trichinellosis prevention and control.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"7"},"PeriodicalIF":3.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972338","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}
Giorgia Di Muro, Carlotta Tessarolo, Giulia Cagnotti, Alessandra Favole, Sara Ferrini, Ugo Ala, Claudio Bellino, Giuliano Borriello, Marina Gallo, Giulia Iamone, Barbara Iulini, Marzia Pezzolato, Cristina Casalone, Maria Caramelli, Lorenzo Capucci, Patrizia Cavadini, Cristiano Corona, Antonio D'Angelo
{"title":"Neurofilament light chain (Nf-L) in cerebrospinal fluid and serum as a potential biomarker in the differential diagnosis of neurological diseases in cattle.","authors":"Giorgia Di Muro, Carlotta Tessarolo, Giulia Cagnotti, Alessandra Favole, Sara Ferrini, Ugo Ala, Claudio Bellino, Giuliano Borriello, Marina Gallo, Giulia Iamone, Barbara Iulini, Marzia Pezzolato, Cristina Casalone, Maria Caramelli, Lorenzo Capucci, Patrizia Cavadini, Cristiano Corona, Antonio D'Angelo","doi":"10.1186/s13567-024-01441-4","DOIUrl":"10.1186/s13567-024-01441-4","url":null,"abstract":"<p><p>Neurofilament light chain (Nf-L) is a biomarker for axonal damage in human neurology but is understudied in cattle. With this study we wanted to determine Nf-L stability at two different storage temperatures and Nf-L levels in healthy cattle and the relationship with age, evaluate whether Nf-L holds diagnostic potential for neurological disorders, and whether an association exists between Nf-L in serum and in cerebrospinal fluid (CSF). To do this, we measured Nf-L levels in CSF and serum samples from 49 healthy and 75 sick cattle. Storage at -80 °C or -20 °C had no impact on Nf-L concentration. Physiological median Nf-L levels were 6.3 pg/mL (serum) and 414 pg/mL (CSF) in calves and 5.5 pg/mL (serum) and 828 pg/mL (CSF) in adult cattle. There was no association between Nf-L levels in CSF and calf age (r<sup>2</sup> 0.07, p = 0.13), while a weak association was found for Nf-L in serum (r<sup>2</sup> 0.26, p = 0.01), and a significant association in adult cattle (CSF, r<sup>2</sup> 0.69, p = 0.0001; serum, r<sup>2</sup> 0.68, p = 0.0003). CSF Nf-L levels were higher in samples from animals with degenerative (median Nf-L 49971 pg/mL) and infectious central nervous system (CNS) disorders (median Nf-L, age < 2 months 8863 pg/mL; age 2-12 months 17474 pg/mL; age 1-6 years 3546 pg/mL), CNS anomalies and metabolic/toxic disorders. There was a significant association between CSF Nf-L and serum Nf-L in cattle with neurological disorders (r<sup>2</sup> 0.2, p = 0.009). Taken together, these findings suggest the potential of Nf-L as a diagnostic tool in cattle neurology.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"6"},"PeriodicalIF":3.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967099","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}
Nam Phuong Le, Bac Tran Le, Van Phan Le, Jung-Eun Park
{"title":"Molecular characterization of swine acute diarrhea syndrome coronavirus detected in Vietnamese pigs.","authors":"Nam Phuong Le, Bac Tran Le, Van Phan Le, Jung-Eun Park","doi":"10.1186/s13567-024-01445-0","DOIUrl":"10.1186/s13567-024-01445-0","url":null,"abstract":"<p><p>Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine coronavirus that was recently identified in southern China in 2017. At present, there is a lack of nationwide epidemiological investigations of the newly emerged SADS-CoV. Because Vietnam is geographically adjacent to southern China, many diseases have spread from China to Vietnam. To assess SADS-CoV transmission to Vietnam, we conducted a retrospective study to detect SADS-CoV in samples collected from pig farms in northern Vietnam. Among the 69 fecal samples tested, 5 were positive for SADS-CoV. The spike gene sequence showed high genetic homology with strains circulating in China. Our study is the first to show that SADS-CoV has spread from China to Vietnam and highlights the need for global epidemiological investigations of SADS-CoV.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"4"},"PeriodicalIF":3.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955871","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}
Fei Zhao, Xiao Cong, Xiaobo Huang, Yi Zheng, Qin Zhao, Yiping Wen, Rui Wu, Senyan Du, Sanjie Cao, Feng Cong, Yiping Wang
{"title":"Interplay of swine acute diarrhoea syndrome coronavirus and the host intrinsic and innate immunity.","authors":"Fei Zhao, Xiao Cong, Xiaobo Huang, Yi Zheng, Qin Zhao, Yiping Wen, Rui Wu, Senyan Du, Sanjie Cao, Feng Cong, Yiping Wang","doi":"10.1186/s13567-024-01436-1","DOIUrl":"10.1186/s13567-024-01436-1","url":null,"abstract":"<p><p>Swine acute diarrhoea syndrome coronavirus (SADS-CoV), a novel HKU2-related coronavirus of bat origin, is a newly emerged swine enteropathogenic coronavirus that causes severe diarrhoea in piglets. SADS-CoV has a broad cell tropism with the capability to infect a wide variety of cells from human and diverse animals, which implicates its ability to hold high risks of cross-species transmission. The intracellular antiviral immunity, comprised of the intrinsic and innate immunity, represents the first line of host defence against viral infection prior to the onset of adaptive immunity. To date, there are no vaccines and drugs approved to prevent or treat SADS-CoV infection. Understanding of the mutual relationship between SADS-CoV infection and host immunity is crucial for the development of novel vaccines and drugs against SADS-CoV. Here, we review recent advancements in our understanding of the interplay between SADS-CoV infection and the host intrinsic and innate immunity. The extensive and in-depth investigation on their interactive relationship will contribute to the identification of new targets for developing intervention strategies to control SADS-CoV infection.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"5"},"PeriodicalIF":3.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955869","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":"DPV pUL15 possesses a potential NLS, which is important for the location of the terminase complex and for viral proliferation and genome cleavage.","authors":"Qiao Yang, Yaya Feng, Lizhen Liu, Linlin Yang, Mingshu Wang, Ying Wu, Bin Tian, Xumin Ou, Renyong Jia, Dekang Zhu, Shun Chen, Mafeng Liu, Xinxin Zhao, Shaqiu Zhang, Juan Huang, Di Sun, Yu He, Zhen Wu, Ling Zhang, Yanling Yu, Anchun Cheng","doi":"10.1186/s13567-024-01420-9","DOIUrl":"https://doi.org/10.1186/s13567-024-01420-9","url":null,"abstract":"<p><p>In herpesvirus, the terminase subunit pUL15 is involved in cleavage of the viral genome concatemers in the nucleus. Previous studies have shown that herpes simplex virus 1 (HSV-1) pUL15 can enter the nucleus without other viral proteins and help other terminase subunits enter the nucleus. However, this study revealed that duck plague virus (DPV) pUL15 cannot localize independently to the nucleus and can only be localized in the nucleus in the presence of pUL28 and pUL33. However, the data suggested the presence of a potential nuclear localization signal (NLS) in DPV pUL15, which is important for the localization of the terminase subunits. Subsequently, several single-point mutants were constructed to identify the vital amino acids within the NLS. The conserved amino acids K187, R188, and K190 are critical for the nuclear localization of pUL15, pUL28, and pUL33 but not for their interaction. Furthermore, corresponding recombinant viruses were constructed. The results revealed that the mutations rUL15K187Q, rUL15K188Q and rUL15K190Q had an obvious influence on concatemeric genome cleavage, but only K190Q significantly affected the production of progeny virions. These findings indicate that the NLS is important for the functions of DPV pUL15. Overall, a potential NLS and the key amino acids in DPV pUL15 were identified. Mutations in K187, K188 and K190 affected the cleavage of the concatemeric genome, but only mutations in K190 had an obvious effect on viral proliferation.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"3"},"PeriodicalIF":3.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955867","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}
Ram Prasad Aganja, Jun Kwon, Amal Senevirathne, John Hwa Lee
{"title":"Deletion of pagL and arnT genes involved in LPS structure and charge modulation in the Salmonella genome confer reduced endotoxicity and retained efficient protection against wild-type Salmonella Gallinarum challenge in chicken.","authors":"Ram Prasad Aganja, Jun Kwon, Amal Senevirathne, John Hwa Lee","doi":"10.1186/s13567-024-01413-8","DOIUrl":"https://doi.org/10.1186/s13567-024-01413-8","url":null,"abstract":"<p><p>Fowl typhoid (FT) poses a significant threat to the poultry industry and can cause substantial economic losses, especially in developing regions. Caused by Salmonella Gallinarum (SG), vaccination can prevent FT. However, existing vaccines, like the SG9R strain, have limitations, including residual virulence and potential reversion of pathogenicity. This study aims to develop safer and more effective SG vaccine strains through targeted genetic modifications, focusing on genes involved in lipopolysaccharide (LPS) biosynthesis and modification. We evaluated two novel mutant SG strains, JOL3015 and JOL3016, carrying in-frame deletions in ΔlonΔrfaLΔarnT and ΔlonΔrfaLΔpagL, respectively. Intramuscular immunisation of 4-week-old young birds with JOL3015 and JOL3016 strains showed minimal impact on their growth. However, the immunisation significantly increased antigen-specific IgY, sIgA secretion, and CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses while inducing lower pro-inflammatory cytokine levels than SG9R. Histopathological evaluations revealed substantial protection in the immunised birds, with minimal tissue damage and inflammatory responses, thus reducing the in vivo bacterial burden. Furthermore, none of the immunised birds died. This outcome highlights the significant safety and protection the selected genetic modifications conferred. Our results indicate that JOL3016 provided comparable protective outcomes on par with SG9R, yet with significantly lower endotoxicity responses during the lethal challenge with SG WT JOL422. The novel detoxified SG strains, particularly JOL3016, offer a promising alternative to existing vaccines for FT. They provide effective protection with minimal impact on poultry growth, thereby minimising the risks associated with reversion and endotoxicity. The study highlights the potential of genetically engineered vaccine strains in improving poultry health and productivity, emphasising the importance of continued research.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"2"},"PeriodicalIF":3.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhi, Chen Mei, Zhenyi Liu, Ying Liu, Hongjun Wang
{"title":"Glutathione reductase modulates endogenous oxidative stress and affects growth and virulence in Avibacterium paragallinarum.","authors":"Yan Zhi, Chen Mei, Zhenyi Liu, Ying Liu, Hongjun Wang","doi":"10.1186/s13567-024-01388-6","DOIUrl":"10.1186/s13567-024-01388-6","url":null,"abstract":"<p><p>Glutathione reductase (GR) plays a pivotal role in managing oxidative stress, a process crucial for microbial virulence and adaptation, yet it has not been extensively explored in bacteria such as Avibacterium paragallinarum (Av. paragallinarum). This study examined the specific roles of GR in Av. paragallinarum, focusing on how GR modulates the bacterium's response to oxidative stress and impacts its pathogenic behavior. Using gene knockouts together with transcriptomic and metabolomic profiling, we identified an important shift in redox balance due to GR deficiency, which disrupted energy metabolism and weakened the oxidative stress defense, culminating in a notable decline in virulence. In addition, decreased growth rates, reduced biofilm production, and weakened macrophage interactions were observed in GR-deficient strains. Notably, our findings reveal a sophisticated adaptation mechanism wherein the bacterium recalibrated its metabolic pathways in response to GR deficiency without fully restoring virulence. Our in vivo studies further highlight the pivotal role of GR in pathogen fitness. Together, our findings connect GR-mediated redox control to bacterial virulence, thereby furthering the understanding of microbial adaptation and positioning GR as a potential antimicrobial target. Our insights into the GR-centric regulatory network pave the way for leveraging bacterial redox mechanisms in the development of novel antimicrobial therapies, highlighting the importance of oxidative stress management in bacterial pathogenicity.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"1"},"PeriodicalIF":3.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923629","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}
Han Gao, Taoming Gu, Xiaopeng Gao, Zebu Song, Jing Liu, Yi Song, Guihong Zhang, Yankuo Sun
{"title":"African swine fever virus enhances viral replication by increasing intracellular reduced glutathione levels, which suppresses stress granule formation.","authors":"Han Gao, Taoming Gu, Xiaopeng Gao, Zebu Song, Jing Liu, Yi Song, Guihong Zhang, Yankuo Sun","doi":"10.1186/s13567-024-01433-4","DOIUrl":"10.1186/s13567-024-01433-4","url":null,"abstract":"<p><p>African swine fever virus (ASFV) is a DNA virus that has significantly impacted the global swine industry. Currently, there are no effective therapies or vaccines against ASFV. Stress granules (SGs), known for their antiviral properties, are not induced during ASFV infection, even though reactive oxygen species (ROS) are generated. The mechanism by which ASFV regulates SGs formation remains unclear. This study demonstrates that ASFV antagonises SGs formation and increases intracellular levels of reduced glutathione (GSH) levels. The use of the GSH inhibitor BSO and the activator NAC confirmed that the ASFV-induced increase in GSH helps to suppress SGs formation and influences viral replication. Additionally, this study revealed that ASFV enhances GSH by upregulating the antioxidant transcription factor NRF2, as well as factors involved in GSH synthesis and regeneration, such as GCLC, and those related to the ferroptosis pathway, such as SLC7A11. Furthermore, the study uncovered that ASFV manipulates intracellular GSH levels by activating the mitochondrial protein AIFM1. This regulatory mechanism helps the virus inhibit the formation of intracellular SGs, thereby creating an optimal environment for viral replication. These findings provide new insights into the molecular strategies employed by ASFV.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"172"},"PeriodicalIF":3.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872851","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}