{"title":"Novel strategies for PEDV to interfere with host antiviral immunity through Caspase-1.","authors":"Wen Shi, Weilv Xu, Qian Lv, Zi'an Zhang, Xinyu Fu, Danyue Li, Suhui He, Yumeng Wang, Jinxia Xu, Shiyang Liu, Yuanxiang Ge, Peide Li, Changbo Ou, Xiaoliang Li, Fushan Shi","doi":"10.1080/21505594.2025.2560890","DOIUrl":"10.1080/21505594.2025.2560890","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV), a member of the <i>Coronaviridae</i> family, responsible for substantial morbidity and mortality in neonatal piglets, representing an ongoing threat to the swine industry. The type I interferon (IFN) response is integral to the innate immune system, playing a critical role in host defense against viral infection. However, viruses have evolved diverse strategies to evade or suppress host immune responses to facilitate their replication. In this study, we demonstrate that PEDV targets Caspase-1 to enhance its replication and suppress IFN-β production. PEDV infection increases the expression of Caspase-1 in both tissues and cells. Overexpression of Caspase-1 significantly reduces IFN-β production while promoting PEDV replication. The suppression of IFN-β production by Caspase-1 is mediated through the cleavage of mitochondrial antiviral signaling (MAVS). Specifically, Caspase-1 cleaves MAVS at Asp182, facilitating viral replication and inhibiting IFN-β production. The resulting MAVS fragments, once cleaved, lose their ability to both inhibit viral replication and induce IFN-β production, thereby enabling PEDV proliferation. Additionally, we observe that Caspase-1 exhibits species-specific cleavage effects on MAVS, though its impact on MAVS cleavage remains consistent. This study provides a novel target for anti-PEDV therapeutic strategies.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2560890"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058697","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}
VirulencePub Date : 2025-12-01Epub Date: 2025-02-20DOI: 10.1080/21505594.2025.2467156
Qingying Fan, Haikun Wang, Shuo Yuan, Yingying Quan, Rishun Li, Li Yi, Aiqing Jia, Yuxin Wang, Yang Wang
{"title":"Pyruvate formate lyase regulates fermentation metabolism and virulence of <i>Streptococcus suis</i>.","authors":"Qingying Fan, Haikun Wang, Shuo Yuan, Yingying Quan, Rishun Li, Li Yi, Aiqing Jia, Yuxin Wang, Yang Wang","doi":"10.1080/21505594.2025.2467156","DOIUrl":"10.1080/21505594.2025.2467156","url":null,"abstract":"<p><p><i>Streptococcus suis</i>, a zoonotic pathogen, is commonly found as a commensal bacterium in the respiratory tracts of pigs. Under specific conditions, it becomes invasive and enters the blood, causing severe systemic infections. For <i>S. suis</i>, effective acquisition of carbon sources in different host niches is necessary for its survival. However, as of now, our understanding of the metabolism of <i>S. suis</i> within the host is highly restricted. Pyruvate formate lyase (PFL) plays a crucial role in bacterial survival of in glucose-limited and hypoxic host tissues. Here, we investigated the physiological and metabolic functions of PFL PflB in <i>S. suis</i> and elucidated its pivotal role in regulating virulence within the mucosal and blood niches. We demonstrate that PflB is a key enzyme for <i>S. suis</i> to support mixed-acid fermentation under glucose-limited and hypoxic conditions. Additionally, PflB is involved in regulating <i>S. suis</i> morphology and stress tolerance, and its regulation of capsular polysaccharide content depends on dynamic carbon availability. We also found that PflB is associated with the capacity of <i>S. suis</i> to cause bacteremia and persist in the upper respiratory tract to induce persistent infection. Our results provide highly persuasive evidence for the relationship between metabolic regulation and the virulence of <i>S. suis</i>.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2467156"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468937","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":"Alongshan virus: An emerging arboviral challenge in regional health security.","authors":"Meixi Ren, Zheng Pang, Yingxin Tu, Anan Wang, Tao Xu, Xiaoli Yu, Guoyu Niu","doi":"10.1080/21505594.2025.2492360","DOIUrl":"10.1080/21505594.2025.2492360","url":null,"abstract":"<p><p>The Alongshan virus (ALSV), classified within the Flaviviridae family and belonging to the Jingmenvirus group, is a segmented RNA virus that was first identified in China in 2017. Since then, it has been reported in several Eurasian countries. Although no confirmed fatal cases have been documented, the potential public health risks associated with ALSV are significant and warrant serious attention. The emergence of ALSV has not only broadened the array of tick-borne diseases but has also enriched the research landscape surrounding segmented flaviviruses. Despite these advancements, our understanding of ALSV is still nascent, and its complex infection pathways remain largely unexplored. This review seeks to offer an in-depth examination of ALSV, addressing its biological properties, molecular features, epidemiological data, clinical presentations, and diagnostic methodologies. Our objective is to promote progress in the formulation of preventive, diagnostic, and therapeutic measures for this emerging segmented flavivirus.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2492360"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064929","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}
VirulencePub Date : 2025-12-01Epub Date: 2025-05-14DOI: 10.1080/21505594.2025.2503430
Jemima Swain, Isabel Askenasy, Rahan Rudland Nazeer, Pok-Man Ho, Edoardo Labrini, Leonardo Mancini, Qingqing Xu, Franziska Hollendung, Isabella Sheldon, Camilla Dickson, Amelie Welch, Adam Agbamu, Camilla Godlee, Martin Welch
{"title":"Pathogenicity and virulence of <i>Pseudomonas aeruginosa</i>: Recent advances and under-investigated topics.","authors":"Jemima Swain, Isabel Askenasy, Rahan Rudland Nazeer, Pok-Man Ho, Edoardo Labrini, Leonardo Mancini, Qingqing Xu, Franziska Hollendung, Isabella Sheldon, Camilla Dickson, Amelie Welch, Adam Agbamu, Camilla Godlee, Martin Welch","doi":"10.1080/21505594.2025.2503430","DOIUrl":"10.1080/21505594.2025.2503430","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is a model for the study of quorum sensing, protein secretion, and biofilm formation. Consequently, it has become one of the most intensely reviewed pathogens, with many excellent articles in the current literature focusing on these aspects of the organism's biology. Here, though, we aim to take a slightly different approach and consider some less well appreciated (but nonetheless important) factors that affect <i>P. aeruginosa</i> virulence. We start by reminding the reader of the global importance of <i>P. aeruginosa</i> infection and that the \"virulome\" is very niche-specific. Overlooked but obvious questions such as \"what prevents secreted protein products from being digested by co-secreted proteases?\" are discussed, and we suggest how the nutritional preference(s) of the organism might dictate its environmental reservoirs. Recent studies identifying host genes associated with genetic predisposition towards <i>P. aeruginosa</i> infection (and even infection by specific <i>P. aeruginosa</i> strains) and the role(s) of intracellular <i>P. aeruginosa</i> are introduced. We also discuss the fact that virulence is a high-risk strategy and touch on how expression of the two main classes of virulence factors is regulated. A particular focus is on recent findings highlighting how nutritional status and metabolism are as important as quorum sensing in terms of their impact on virulence, and how co-habiting microbial species at the infection site impact on <i>P. aeruginosa</i> virulence (and <i>vice versa</i>). It is our view that investigation of these issues is likely to dominate many aspects of research into this WHO-designated priority pathogen over the next decade.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2503430"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029782","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":"Porcine cGAS-STING signalling induced apoptosis negatively regulates STING downstream IFN response and autophagy via different mechanisms.","authors":"Nengwen Xia, Anjing Liu, Hongjian Han, Sen Jiang, Qi Cao, Jia Luo, Jiajia Zhang, Weilin Hao, Ziyan Sun, Nanhua Chen, Huiling Zhang, Wanglong Zheng, Jianzhong Zhu","doi":"10.1080/21505594.2025.2496436","DOIUrl":"10.1080/21505594.2025.2496436","url":null,"abstract":"<p><p>The innate immune cGAS-STING signalling pathway recognizes double-stranded DNA and induces the interferon (IFN) response, autophagy and apoptosis, exerting a broad antiviral effect. However, the mechanisms and interrelationship between STING induced downstream IFN, autophagy, and apoptosis in livestock have not been fully elucidated. Our previous study defined porcine STING (pSTING) induced IFN, autophagy and apoptosis, and showed that IFN does not affect autophagy and apoptosis, whereas autophagy inhibits both IFN and apoptosis, likely by promoting pSTING degradation. In this study, we further explored the underlying mechanism of pSTING induced apoptosis and the regulation of IFN and autophagy by apoptosis. First, pSTING induces endoplasmic reticulum (ER) stress and mitochondrial damage to activate caspases 9, 3, and 7, which drive intrinsic apoptosis. Second, pSTING triggered apoptosis inhibits the IFN response by activating caspase 7, which cleaves pIRF3 at the species specific D197/D198 site. Third, pSTING activated apoptotic caspases 9, 3, and 7 reduce the expression of ATG proteins, and cleave the ATG5-ATG12L1 complex, effectively inhibiting autophagy. Fourth, knockout of pSTING activated apoptosis heightens the IFN response and autophagy, while suppressing the replication of Herpes Simplex Virus type 1 (HSV-1), Vesicular Stomatitis Virus (VSV) and Pseudorabies Virus (PRV). This study sheds light on the molecular mechanisms of innate immunity in pigs.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2496436"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041558","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}
VirulencePub Date : 2025-12-01Epub Date: 2025-02-15DOI: 10.1080/21505594.2025.2466482
Haixin Bi, Fei Wang, Lin Lin, Dajun Zhang, Menghan Chen, Yuyao Shang, Lin Hua, Huanchun Chen, Bin Wu, Zhong Peng
{"title":"The T-type voltage-gated Ca<sup>2+</sup> channel Ca<sub>V</sub>3.1 involves in the disruption of respiratory epithelial barrier induced by <i>Pasteurella multocida</i> toxin.","authors":"Haixin Bi, Fei Wang, Lin Lin, Dajun Zhang, Menghan Chen, Yuyao Shang, Lin Hua, Huanchun Chen, Bin Wu, Zhong Peng","doi":"10.1080/21505594.2025.2466482","DOIUrl":"10.1080/21505594.2025.2466482","url":null,"abstract":"<p><p><i>Pasteurella multocida</i> toxin (PMT) is an exotoxin produced by several members of the zoonotic respiratory pathogen <i>P. multocida</i>. The role of PMT in disrupting the mammalian respiratory barrier remains to be elucidated. In this study, we showed that inoculation of recombinantly expressed PMT increased the permeability of the respiratory epithelial barrier in mouse and respiratory cell models. This was evidenced by a decreased expression of tight junctions (ZO-1, occludin) and adherens junctions (β-catenin, E-cadherin), as well as enhanced cytoskeletal rearrangement. In mechanism, we demonstrated that PMT inoculation induced cytoplasmic Ca<sup>2+</sup> inflow, leading to an imbalance of cellular Ca<sup>2+</sup> homoeostasis and endoplasmic reticulum stress. This process further stimulated the RhoA/ROCK signalling, promoting cytoskeletal rearrangement and reducing the expression of tight junctions and adherens junctions. Notably, the T-type voltage-gated Ca<sup>2+</sup> channel Ca<sub>V</sub>3.1 was found to participate in PMT-induced cytoplasmic Ca<sup>2+</sup> inflow. Knocking out Ca<sub>V</sub>3.1 significantly reduced the cytotoxicity induced by PMT on swine respiratory epithelial cells and mitigated cytoplasmic Ca<sup>2+</sup> inflow stimulated by PMT. These findings suggest Ca<sub>V</sub>3.1 contributes to PMT-induced respiratory epithelial barrier disruption.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2466482"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415134","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}
VirulencePub Date : 2025-12-01Epub Date: 2025-04-15DOI: 10.1080/21505594.2025.2491650
Gabriela Fior Ribeiro, Emily L Priest, Helen Heaney, Jonathan P Richardson, Delma S Childers
{"title":"Mannan is a context-dependent shield that modifies virulence in <i>Nakaseomyces glabratus</i>.","authors":"Gabriela Fior Ribeiro, Emily L Priest, Helen Heaney, Jonathan P Richardson, Delma S Childers","doi":"10.1080/21505594.2025.2491650","DOIUrl":"10.1080/21505594.2025.2491650","url":null,"abstract":"<p><p>Fungal-host interaction outcomes are influenced by how the host recognizes fungal cell wall components. Mannan is a major cell wall carbohydrate and can be a glycoshield that blocks the inner cell wall β-1,3-glucan from activating pro-inflammatory immune responses. Disturbing this glycoshield in <i>Candida albicans</i> results in enhanced antifungal host responses and reduced fungal virulence. However, deletions affecting mannan synthesis can lead to systemic hypervirulence for <i>Nakaseomyces glabratus</i> (formerly <i>Candida glabrata</i>) suggesting that proper mannan architecture dampens virulence for this organism. <i>N. glabratus</i> is the second leading cause of invasive and superficial candidiasis, but little is known about how the cell wall affects <i>N. glabratus</i> pathogenesis. In order to better understand the importance of these species-specific cell wall adaptations in infection, we set out to investigate how the mannan polymerase II complex gene, <i>MNN10</i>, contributes to <i>N. glabratus</i> cell wall architecture, immune recognition, and virulence in reference strains BG2 and CBS138. <i>mnn10</i>Δ cells had thinner inner and outer cell wall layers and elevated mannan, chitin, and β-1,3-glucan exposure compared to wild-type cells. Consistent with these observations, <i>mnn10</i>Δ cells activated the β-1,3-glucan receptor in oral epithelial cells (OECs), EphA2, and caused less OEC damage than wild-type. <i>mnn10</i>Δ replication was also restricted in macrophages compared to wild-type controls. Yet, during systemic infection in <i>Galleria mellonella</i> larvae, <i>mnn10</i>Δ cells induced rapid larval melanization and BG2 <i>mnn10</i>Δ cells killed larvae significantly faster than wild-type. Thus, our data suggest that mannan plays context-dependent roles in <i>N. glabratus</i> pathogenesis, acting as a glycoshield in superficial disease models and modulating virulence during systemic infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2491650"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001362","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}
VirulencePub Date : 2025-12-01Epub Date: 2024-12-26DOI: 10.1080/21505594.2024.2439497
Carol Uphoff Meteyer, Justin G Boyles
{"title":"Fungal chimera: A lethal mammalian fungus with invasion strategies of plant pathogens.","authors":"Carol Uphoff Meteyer, Justin G Boyles","doi":"10.1080/21505594.2024.2439497","DOIUrl":"https://doi.org/10.1080/21505594.2024.2439497","url":null,"abstract":"","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2439497"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898482","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}
VirulencePub Date : 2025-12-01Epub Date: 2025-08-28DOI: 10.1080/21505594.2025.2545570
Jingrou Chen, Jingchun Fang, Li Sun, Zongjun Zhang, Qinghua Ma, Jiahao Wu, Yili Chen, Kang Liao, Tiandi Long, Hongxu Xu
{"title":"Multiple concurrent opportunistic infections in patient with myasthenia gravis: A case report.","authors":"Jingrou Chen, Jingchun Fang, Li Sun, Zongjun Zhang, Qinghua Ma, Jiahao Wu, Yili Chen, Kang Liao, Tiandi Long, Hongxu Xu","doi":"10.1080/21505594.2025.2545570","DOIUrl":"https://doi.org/10.1080/21505594.2025.2545570","url":null,"abstract":"<p><p>Myasthenia gravis (MG), a rare autoimmune disorder with poor prognosis, especially when complicated by opportunistic infections, which pose significant risks in clinical practice. We aimed to analyse a clinical case of a middle-aged male patient with MG, who developed severe lower gastrointestinal bleeding and multiple opportunistic infections post-immunosuppressive therapy. This case report is based on comprehensive clinical evaluations, including colonoscopy, histopathological examination, bronchoscopy, bronchoalveolar lavage (BAL), and metagenomic next-generation sequencing (mNGS). The patient exhibited persistent ptosis and pulmonary infection, and was treated with Meropenem 12 mg once daily (qd), Tacrolimus 2 mg qd, and Bromhexine 60 mg three times daily (tid). Due to ongoing lower gastrointestinal bleeding, surgery was performed. Colonoscopy revealed multiple ulcers, with histopathology confirming Cytomegalovirus (CMV) and Histoplasmosis infections. Bronchoalveolar lavage fluid (BALF) identified infections with Aspergillus fumigatus, Talaromyces, and Stenotrophomonas maltophilia. mNGS further detected Pneumocystis jirovecii. Based on these findings, the treatment plan was adjusted to include Amphotericin B complex 25 mg via intravenous (IV) qd, Tigecycline 100 mg q12h, and Sulfamethoxazole (SMZ) 0.96 g q6h for anti-infection, along with Ganciclovir 250 mg IV q12h. The patient continues to receive infusions of immunoglobulins and albumin. This case underscores the importance of monitoring MG patients on immunosuppressive therapy for opportunistic infections, emphasizing the complexity of managing multiple pathogens simultaneously.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2545570"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971288","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}