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Porcine reproductive and respiratory syndrome virus nsp6 hijacks ATP1B1 antagonizing TRAF6 mediated antiviral innate immunity 猪繁殖与呼吸综合征病毒nsp6劫持ATP1B1,拮抗TRAF6介导的抗病毒先天免疫。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1016/j.vetmic.2025.110803
Haotian Yang , Han Gu , He Qiu , Bicheng Li , Jidong Xu , Tong Cao , Du Liuyang , Xiaoliang Li , Fang He
Porcine reproductive and respiratory syndrome virus (PRRSV) is an immune-suppressive pathogen that poses a significant challenge to the global swine industry. The mechanism by which PRRSV regulating host inflammation to evade innate immunity remains unclear. Here, Na+ /K+-ATPase beta1 subunit (ATP1B1), a pivotal antiviral protein, was shown to interact with PRRSV nsp6, a tiny viral protein encoded by ORF1a. ATP1B1 stabilized the protein level of TRAF6 by downregulating K48-linked ubiquitination of TRAF6, thus triggering NF-κB signaling and inflammatory response. Moreover, PRRSV nsp6 competetively interacted with ATP1B1 via the site of Leu 3 and impaired the formation of ATP1B1-TRAF6 complex, leading to TRAF6 proteasomal degradation and compromised inflammatory response. PRRSV with the corresponding mutation in nsp6 L3S was successfully rescued but presented defective virus growth in the late stage of infection, especially under the inflammation condition induced by either ATP1B1 overexpression or poly (I:C) stimulation. In addition, the halt in PRRSV replication was induced by treatment with autophagy inhibitor BafA1 during virus passage. L3S mutant virus impaired the recovery of virus growth even after the removal of BafA1, indicating the key role of nsp6 in sustaining virus vitality under innate immunity. Taken together, these results elucidate the functional mechanism by which PRRSV alleviates the inflammatory response to promote successful virus proliferation and growth recovery from the host innate immune response.
猪繁殖与呼吸综合征病毒(PRRSV)是一种免疫抑制病原体,对全球养猪业构成了重大挑战。PRRSV调节宿主炎症以逃避先天免疫的机制尚不清楚。在这里,Na+ /K+-ATPase beta1亚基(ATP1B1)是一种关键的抗病毒蛋白,被证明与PRRSV nsp6(一种由ORF1a编码的微小病毒蛋白)相互作用。ATP1B1通过下调k48相关的TRAF6泛素化来稳定TRAF6蛋白水平,从而触发NF-κB信号传导和炎症反应。此外,PRRSV nsp6通过Leu 3位点与ATP1B1竞争性相互作用,破坏ATP1B1-TRAF6复合物的形成,导致TRAF6蛋白酶体降解和炎症反应受损。具有相应nsp6 L3S突变的PRRSV成功获救,但在感染后期出现病毒生长缺陷,特别是在ATP1B1过表达或poly (I:C)刺激诱导的炎症条件下。此外,在病毒传代过程中,用自噬抑制剂BafA1处理可诱导PRRSV复制停止。L3S突变病毒即使在去除BafA1后也破坏了病毒生长的恢复,这表明nsp6在先天免疫下维持病毒活力的关键作用。综上所述,这些结果阐明了PRRSV通过减轻炎症反应来促进宿主先天免疫反应中病毒增殖和生长恢复的功能机制。
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引用次数: 0
Corrigendum to “ASFV activates STAT3 to induce proviral M2 macrophage polarization” [Vet. Microbiol. 311 (2025) 110733] “ASFV激活STAT3诱导病毒前M2巨噬细胞极化”的勘误。微生物学。311 (2025)110733 [j]
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-08 DOI: 10.1016/j.vetmic.2025.110833
Yanru Chen , Haowei Chen , Weijia Zhang , Penghao Lv , Zhichao Wang , Hanlin Liao , Kaiyue Wei , Qigai He , Min Cui
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引用次数: 0
The Streptococcus suis ble gene does not encode a functional bleomycin resistance protein 猪链球菌ble基因不编码功能性的博来霉素抗性蛋白
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-20 DOI: 10.1016/j.vetmic.2025.110769
Ashley Belinfante , Janel Kolar , Sarah M. Shore , Tracy L Nicholson
A high prevalence of acquired bleomycin resistance has been reported in both clinical and non-clinical settings. Streptococcus suis is a zoonotic swine pathogen capable of causing a spectrum of clinical disease outcomes in both pigs and humans and contributes to significant economic losses to the swine industry worldwide. A recent report evaluating the genomic diversity of S. suis isolates obtained from within the U.S. identified a ble gene predicted to encode a bleomycin resistance protein in all isolates evaluated. The goal of this study was to compare the amino acid sequence similarity among the predicted S. suis bleomycin resistance proteins and to functionally test the predicted ble gene allelic variants for the ability to confer bleomycin resistance. A high degree of similarity was observed among the predicted S. suis bleomycin resistance proteins. However, a weak similarity was observed in comparison to other well-characterized bleomycin resistance proteins. All tested S. suis strains exhibited phenotypic resistance to bleomycin. However, none of the S. suis ble genes tested encoded a functional bleomycin resistance protein capable of conferring resistance to bleomycin or bleomycin-like molecules.
据报道,在临床和非临床环境中,获得性博莱霉素耐药的发生率很高。猪链球菌是一种人畜共患的猪病原体,能够在猪和人身上引起一系列临床疾病,并对全球养猪业造成重大经济损失。最近的一份报告评估了从美国获得的猪链球菌分离株的基因组多样性,在所有被评估的分离株中发现了一个可编码博来霉素抗性蛋白的ble基因。本研究的目的是比较预测的猪链球菌博来霉素耐药蛋白之间的氨基酸序列相似性,并对预测的ble基因等位基因变异进行功能测试,以确定博来霉素耐药的能力。预测的猪链球菌博莱霉素耐药蛋白高度相似。然而,与其他具有良好特征的博莱霉素耐药蛋白相比,观察到微弱的相似性。所有猪链球菌均表现出对博来霉素的表型抗性。然而,测试的s.s suisble基因都没有编码功能性的博来霉素抗性蛋白,能够赋予对博来霉素或博来霉素样分子的抗性。
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引用次数: 0
Neuromedin B and its receptor NMBR inhibit H9N2 infection 神经毒素B及其受体NMBR抑制H9N2感染
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1016/j.vetmic.2025.110790
Guihong Yang , Shimao Tian , Jinyu Yang , Yubing Tang , Ke Tian , Song Wang , Yinli Bao
Neuromedin B (NMB) and its receptor NMBR constitute a neuropeptide system implicated in various physiological processes. While previously associated with innate immunity, their precise antiviral action against influenza A virus (IAV) infection have remained poorly defined. Here, we elucidate the function of the NMB/NMBR axis in the host defense against H9N2 influenza virus. We demonstrate that NMB treatment and NMBR overexpression potentiate IFN-β production and restrict viral replication in H9N2-infected A549 cells and mouse lungs. Conversely, NMBR knockdown compromises the antiviral response, diminishing IFN-β expression and enhancing viral propagation. We further show that NMB/NMBR signaling targets the viral non-structural protein 1 (NS1) by upregulating the E3 ubiquitin ligase TRIM25. Mechanistically, NMB/NMBR activation engages a positive feedback loop with the retinoic acid-inducible gene I (RIG-I) pathway, reinforcing RIG-I activation through enhanced K63-linked ubiquitination while transcriptionally repressing the deubiquitinase CYLD. Consequently, this augmented signaling potentiates the JAK-STAT1 pathway, leading to increased STAT1 phosphorylation and elevated expression of interferon-stimulated gene 15 (ISG15). Our findings establish that the NMB/NMBR axis confers protection against H9N2 IAV by amplifying RIG-I-mediated innate immunity and facilitating NS1 suppression, revealing a pivotal neuroimmune mechanism and suggesting a promising target for developing broad-spectrum, host-directed therapeutics against IAV.
神经肽B (Neuromedin B, NMB)及其受体NMBR构成了一个参与多种生理过程的神经肽系统。虽然以前与先天免疫有关,但它们对甲型流感病毒(IAV)感染的确切抗病毒作用仍然不明确。在此,我们阐明了NMB/NMBR轴在宿主防御H9N2流感病毒中的作用。我们证明NMB处理和NMBR过表达增强了h9n2感染的A549细胞和小鼠肺中IFN-β的产生并限制了病毒的复制。相反,NMBR敲低会损害抗病毒反应,降低IFN-β表达并增强病毒传播。我们进一步发现NMB/NMBR信号通过上调E3泛素连接酶TRIM25靶向病毒非结构蛋白1 (NS1)。在机制上,NMB/NMBR激活与维甲酸诱导基因I (RIG-I)通路形成正反馈回路,通过增强k63相关的泛素化而增强RIG-I激活,同时转录抑制去泛素化酶CYLD。因此,这种增强的信号通路增强了JAK-STAT1通路,导致STAT1磷酸化增加和干扰素刺激基因15 (ISG15)的表达升高。我们的研究结果表明,NMB/NMBR轴通过放大rig - i介导的先天免疫和促进NS1抑制来保护H9N2 IAV,揭示了一个关键的神经免疫机制,并为开发广谱、宿主导向的IAV治疗提供了一个有希望的靶点。
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引用次数: 0
Unveiling the Presence of Coxiella-like bacteria in Rhipicephalus microplus Ticks from Punjab, North India: A 16S rRNA metagenomic study 揭示印度北部旁遮普省微型鼻头蜱中存在柯希拉样细菌:16S rRNA宏基因组研究
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-07 DOI: 10.1016/j.vetmic.2025.110783
Vikas Sharma , Shriya Goel , Kamlesh Bisht , Taruna Kaura , Salony Verma , Abhishek Mewara , Gagandeep Singh Grover , Manisha Biswal
In this study, using 16S rRNA gene-based metagenomics, we aimed to determine the presence of infectious bacteria in the ticks collected from Punjab state in north India. Tick samples were collected from the domesticated animals from the Patiala, Ropar, and Mohali districts of Punjab, India from February 2022- April 2022. DNA was extracted, and the library was prepared by targeting the V3–V4 hypervariable region of the 16S rRNA gene. The sequencing was conducted in Illumina using the 300 bp paired-end chemistry. Eight tick samples were analyzed from the Patiala, Ropar and Mohali districts of Punjab, India, revealing a diverse range of bacterial species within the tick microbiome. Seven out of eight samples were found to harbour Coxiella-like bacteria (46–181,607 reads; closely related to C. burnetii based on 16S rRNA [V3–V4] sequence similarity), indicating their abundance in the tick population. Furthermore, the analysis uncovered the presence of other pathogenic bacterial genera, including Staphylococcus, Streptococcus, Corynebacterium, Enterococcus, Pseudomonas, Bordetella, and Micrococcus in the tick microbiome, highlighting the abundance and diversity of infectious organisms within ticks. 16S rRNA gene-based metagenomics enables valuable insights into infectious agents in disease-transmitting vectors. Coxiella-like bacteria were found to be predominant bacterial species in the tick microbiomes in this study. The public health significance of this finding in animals and humans needs to be explored in this region. However, as 16S rRNA sequencing offers limited resolution for distinguishing closely related taxa, further confirmation using additional loci or whole-genome sequencing is warranted.
本研究采用基于16S rRNA基因的宏基因组学方法,对采集自印度北部旁遮普邦的蜱虫进行感染性细菌的检测。从2022年2月至2022年4月从印度旁遮普省的帕蒂亚拉、罗帕尔和莫哈里地区的家畜身上采集蜱虫样本。提取DNA,针对16S rRNA基因的V3-V4高变区制备文库。测序在Illumina中使用300 bp对端化学进行。对来自印度旁遮普省帕蒂亚拉、罗帕尔和莫哈里地区的8个蜱虫样本进行了分析,揭示了蜱虫微生物组中的多种细菌种类。8份样本中有7份含有科西拉样细菌(46-181,607份,基于16S rRNA [V3-V4]序列相似性,与伯纳氏蜱密切相关),表明其在蜱虫种群中的丰度。此外,分析还发现蜱虫微生物群中存在其他致病性细菌属,包括葡萄球菌、链球菌、棒状杆菌、肠球菌、假单胞菌、博德特拉菌和微球菌,突出了蜱虫体内感染性生物的丰富性和多样性。基于16S rRNA基因的宏基因组学能够对疾病传播载体中的感染因子提供有价值的见解。本研究发现,科希拉样细菌是蜱虫微生物群中的优势菌种。这一发现对动物和人类的公共卫生意义需要在该地区进行探索。然而,由于16S rRNA测序在区分密切相关的分类群方面提供了有限的分辨率,因此需要使用额外的位点或全基因组测序来进一步确认。
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引用次数: 0
Clostridium perfringens can promote the formation of fatty liver in cows 产气荚膜梭菌能促进奶牛脂肪肝的形成。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-05 DOI: 10.1016/j.vetmic.2025.110826
Haolong Wang , Congzhu , Junhui Wang , Xuan Lin , YuYang Guo , Faisal Ayub Kiani , Xiaoshu Zhou , Yi Ding
During the periparturient period, reduced feed intake often causes negative energy balance in dairy cows, leading to fat mobilization, hepatic lipid accumulation, and fatty liver disease (FLD), ultimately compromising health and milk production. This study investigated the association between FLD and gut microbiota dysbiosis, with a particular focus on the role of Clostridium perfringens within the gut–liver axis.
Metagenomic sequencing of ileal contents revealed a marked decrease in microbial diversity in cows with FLD, along with increased abundances of potential pathogens such as C. perfringens, Enterobacter cloacae, and Vibrio alginolyticus. Functional annotation indicated elevated expression of virulence factors (e.g., Hsp60, flagella, mu-toxin), antibiotic resistance genes (e.g., otrA, lsaC), and pathways related to lipopolysaccharide (LPS) biosynthesis and mitogen-activated protein kinase (MAPK) signaling pathways, suggesting enhanced pro-inflammatory potential. qPCR analysis of ileal tissue demonstrated reduced expression of tight junction proteins (zona occludens 1 (ZO-1), Claudin-1, and Occludin) and increased levels of pro-inflammatory cytokines (Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α)), alongside a decrease in the anti-inflammatory cytokine interleukin-10 (IL-10), indicating compromised intestinal barrier function and local inflammation.
Given the significant enrichment of C. perfringens in the ileum of FLD cows, we hypothesized its involvement in disease pathogenesis. To test this, C. perfringens was isolated and orally administered to antibiotic-pretreated mice fed a high-fat diet. These mice developed exacerbated hepatic steatosis, metabolic disturbances, and heightened inflammatory responses. Moreover, Western blot analysis revealed reduced expression of intestinal tight junction proteins (ZO-1, Claudin-1, Occludin), indicating increased intestinal permeability. Quantitative PCR confirmed upregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and downregulation of IL-10 in both intestinal and hepatic tissues. These findings indicate that C. perfringens may promote FLD by impairing gut barrier integrity and enhancing inflammatory responses.
In conclusion, our findings suggest that C. perfringens may contribute to the development of FLD in dairy cows by impairing intestinal barrier integrity and promoting systemic inflammation.
围产期采食量减少往往导致奶牛能量负平衡,导致脂肪动员、肝脏脂质积累和脂肪肝(FLD),最终影响健康和产奶量。本研究调查了FLD与肠道微生物群失调之间的关系,特别关注产气荚膜梭菌在肠-肝轴中的作用。回肠内容物的宏基因组测序显示,患有FLD的奶牛的微生物多样性显著降低,潜在病原体如产气荚膜梭菌、阴沟肠杆菌和溶藻弧菌的丰度增加。功能注释表明,毒力因子(如Hsp60、鞭毛、mu-toxin)、抗生素抗性基因(如otrA、lsaC)以及与脂多糖(LPS)生物合成和丝裂原活化蛋白激酶(MAPK)信号通路相关的途径表达升高,表明促炎潜能增强。qPCR分析显示,回肠组织紧密连接蛋白(闭塞带1 (ZO-1)、Claudin-1和Occludin)的表达减少,促炎细胞因子(白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α))水平升高,同时抗炎细胞因子白细胞介素-10 (IL-10)水平降低,表明肠道屏障功能受损和局部炎症。考虑到产气荚膜荚膜杆菌在FLD奶牛回肠中的显著富集,我们假设它参与了疾病的发病机制。为了验证这一点,研究人员分离出产气荚膜梭菌,并将其口服给喂食高脂肪饮食的抗生素预处理小鼠。这些小鼠的肝脏脂肪变性、代谢紊乱和炎症反应加剧。此外,Western blot分析显示肠道紧密连接蛋白(ZO-1, Claudin-1, Occludin)表达减少,表明肠道通透性增加。定量PCR证实,在肠道和肝脏组织中,促炎细胞因子(IL-1β、IL-6、TNF-α)上调,IL-10下调。这些发现表明产气荚膜原梭菌可能通过破坏肠道屏障完整性和增强炎症反应来促进FLD。综上所述,我们的研究结果表明,产气荚膜杆菌可能通过破坏肠道屏障完整性和促进全身炎症来促进奶牛FLD的发展。
{"title":"Clostridium perfringens can promote the formation of fatty liver in cows","authors":"Haolong Wang ,&nbsp;Congzhu ,&nbsp;Junhui Wang ,&nbsp;Xuan Lin ,&nbsp;YuYang Guo ,&nbsp;Faisal Ayub Kiani ,&nbsp;Xiaoshu Zhou ,&nbsp;Yi Ding","doi":"10.1016/j.vetmic.2025.110826","DOIUrl":"10.1016/j.vetmic.2025.110826","url":null,"abstract":"<div><div>During the periparturient period, reduced feed intake often causes negative energy balance in dairy cows, leading to fat mobilization, hepatic lipid accumulation, and fatty liver disease (FLD), ultimately compromising health and milk production. This study investigated the association between FLD and gut microbiota dysbiosis, with a particular focus on the role of <em>Clostridium perfringens</em> within the gut–liver axis.</div><div>Metagenomic sequencing of ileal contents revealed a marked decrease in microbial diversity in cows with FLD, along with increased abundances of potential pathogens such as <em>C. perfringens</em>, <em>Enterobacter cloacae</em>, and <em>Vibrio alginolyticus</em>. Functional annotation indicated elevated expression of virulence factors (e.g., Hsp60, flagella, mu-toxin), antibiotic resistance genes (e.g., <em>otrA</em>, <em>lsaC</em>), and pathways related to lipopolysaccharide (LPS) biosynthesis and mitogen-activated protein kinase (MAPK) signaling pathways, suggesting enhanced pro-inflammatory potential. qPCR analysis of ileal tissue demonstrated reduced expression of tight junction proteins (zona occludens 1 (ZO-1), Claudin-1, and Occludin) and increased levels of pro-inflammatory cytokines (Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α)), alongside a decrease in the anti-inflammatory cytokine interleukin-10 (IL-10), indicating compromised intestinal barrier function and local inflammation.</div><div>Given the significant enrichment of <em>C. perfringens</em> in the ileum of FLD cows, we hypothesized its involvement in disease pathogenesis. To test this, <em>C. perfringens</em> was isolated and orally administered to antibiotic-pretreated mice fed a high-fat diet. These mice developed exacerbated hepatic steatosis, metabolic disturbances, and heightened inflammatory responses. Moreover, Western blot analysis revealed reduced expression of intestinal tight junction proteins (ZO-1, Claudin-1, Occludin), indicating increased intestinal permeability. Quantitative PCR confirmed upregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and downregulation of IL-10 in both intestinal and hepatic tissues. These findings indicate that <em>C. perfringens</em> may promote FLD by impairing gut barrier integrity and enhancing inflammatory responses.</div><div>In conclusion, our findings suggest that <em>C. perfringens</em> may contribute to the development of FLD in dairy cows by impairing intestinal barrier integrity and promoting systemic inflammation.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"312 ","pages":"Article 110826"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
APPV NS5A employs PKR activation to redirect IRF3 phosphorylation from Ser396 to Ser386, ultimately resulting in the inhibition of IFN production APPV NS5A通过PKR激活将IRF3的磷酸化从Ser396重定向到Ser386,最终抑制IFN的产生
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-12-08 DOI: 10.1016/j.vetmic.2025.110830
Yingjie Xiang , Yongchen Ji , Jingwen Zhao , Huiguang Wu
Atypical porcine pestivirus (APPV) is an emerging pathogen that poses a significant threat to the global swine industry. The nonstructural protein 5 A (NS5A) of Flavivirus is a known immunomodulator; however, its precise role in APPV pathogenesis, particularly its interaction with host interferon (IFN) responses, remains poorly understood. This study elucidates a novel molecular mechanism by which APPV NS5A manipulates host IFN production. We demonstrate that APPV NS5A exerts a dual effect on the phosphorylation of interferon regulatory factor 3 (IRF3): it inhibits the phosphorylation of IRF3 at Ser396 by disrupting the formation of the TBK1-IKKε-IRF3 complex, while simultaneously promoting the interaction between PKR and IRF3 by inducing PKR activation, ultimately resulting in the phosphorylation of IRF3 at Ser386. This phosphorylation switch consequently inhibits the production of IFN. Our research provides critical insights into the immune evasion strategies and pathogenic mechanisms of APPV, identifying the NS5A-PKR-IRF3 axis as a potential therapeutic target for developing novel antiviral interventions.
非典型猪瘟病毒(APPV)是一种新兴病原体,对全球养猪业构成重大威胁。黄病毒非结构蛋白5 A (NS5A)是一种已知的免疫调节剂;然而,其在APPV发病机制中的确切作用,特别是其与宿主干扰素(IFN)反应的相互作用,仍然知之甚少。本研究阐明了APPV NS5A调控宿主IFN产生的一种新的分子机制。我们发现APPV NS5A对干扰素调节因子3 (IRF3)的磷酸化具有双重作用:通过破坏TBK1-IKKε-IRF3复合物的形成,抑制IRF3在Ser396位点的磷酸化;同时通过诱导PKR活化,促进PKR与IRF3的相互作用,最终导致IRF3在Ser386位点的磷酸化。这种磷酸化开关因此抑制IFN的产生。我们的研究为APPV的免疫逃避策略和致病机制提供了重要的见解,确定了NS5A-PKR-IRF3轴作为开发新型抗病毒干预措施的潜在治疗靶点。
{"title":"APPV NS5A employs PKR activation to redirect IRF3 phosphorylation from Ser396 to Ser386, ultimately resulting in the inhibition of IFN production","authors":"Yingjie Xiang ,&nbsp;Yongchen Ji ,&nbsp;Jingwen Zhao ,&nbsp;Huiguang Wu","doi":"10.1016/j.vetmic.2025.110830","DOIUrl":"10.1016/j.vetmic.2025.110830","url":null,"abstract":"<div><div>Atypical porcine pestivirus (APPV) is an emerging pathogen that poses a significant threat to the global swine industry. The nonstructural protein 5 A (NS5A) of Flavivirus is a known immunomodulator; however, its precise role in APPV pathogenesis, particularly its interaction with host interferon (IFN) responses, remains poorly understood. This study elucidates a novel molecular mechanism by which APPV NS5A manipulates host IFN production. We demonstrate that APPV NS5A exerts a dual effect on the phosphorylation of interferon regulatory factor 3 (IRF3): it inhibits the phosphorylation of IRF3 at Ser396 by disrupting the formation of the TBK1-IKKε-IRF3 complex, while simultaneously promoting the interaction between PKR and IRF3 by inducing PKR activation, ultimately resulting in the phosphorylation of IRF3 at Ser386. This phosphorylation switch consequently inhibits the production of IFN. Our research provides critical insights into the immune evasion strategies and pathogenic mechanisms of APPV, identifying the NS5A-PKR-IRF3 axis as a potential therapeutic target for developing novel antiviral interventions.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"312 ","pages":"Article 110830"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR/Cas9-generated CD46-knockout spermatogonial stem cells reveal mechanisms of BVDV-induced reproductive dysfunction in male livestock CRISPR/ cas9产生的敲除cd46的精原干细胞揭示了bvdv诱导雄性牲畜生殖功能障碍的机制
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-16 DOI: 10.1016/j.vetmic.2025.110807
Jiannan Li , Xueting Li , Xiao Li , Wenjie Xu , Liming Yuan , Hongzhao Shi , Zuo Lei , Na Li , Yulei Wei , Jinlian Hua
Bovine viral diarrhea virus (BVDV) is a major viral pathogen that affects ruminants, resulting in significant economic losses due to issues such as immunosuppression, reproductive disorders, and growth retardation. Bulls infected with this virus may become infertile within a few months and can transmit the virus to susceptible cattle during mating. However, the mechanism of BVDV impairing the reproductive function of male livestock is not clear, as there is no suitable cell model. This study used spermatogonial stem cells(SSCs) from cattle and goats as research materials to explore the mechanism by which BVDV affects the reproductive function of male livestock. The results of this study indicate that both cytopathic (cp) and noncytopathic (ncp) BVDV can replicate in SSCs and that SSCs are capable of producing infectious BVDV. Giemsa staining showed significant changes in the morphology of SSCs after BVDV infection. Western blot and mRNA analysis showed that proliferation-related genes (PCNA, CCND1, CDK2) and SSC functional genes (Lin28A, OCT4, SOX2) were down regulated after infection. In addition, BVDV infection can induce ferroptosis in SSCs. Furthermore, CRISPR-Cas9 mediated editing of CD46 in goat SSCs resulted in a decrease in BVDV infection rate and alleviated the negative impact of the virus on cell survival and proliferation. This study provides new insights into the mechanism of reduced reproductive function in male livestock infected with BVDV, and lays the foundation for developing targeted disease resistant breeding strategies.
牛病毒性腹泻病毒(Bovine viral diarrhea virus, BVDV)是一种影响反刍动物的主要病毒性病原体,由于免疫抑制、生殖障碍和生长迟缓等问题而造成重大经济损失。感染这种病毒的公牛可能在几个月内不育,并可在交配期间将病毒传染给易感的牛。然而,由于没有合适的细胞模型,BVDV损害雄性牲畜生殖功能的机制尚不清楚。本研究以牛、山羊精原干细胞(SSCs)为研究材料,探讨BVDV对雄性牲畜生殖功能的影响机制。本研究结果表明,细胞病变(cp)和非细胞病变(ncp) BVDV都可以在SSCs中复制,并且SSCs能够产生感染性BVDV。吉姆萨染色显示BVDV感染后SSCs形态发生显著变化。Western blot和mRNA分析显示,感染后增殖相关基因PCNA、CCND1、CDK2和SSC功能基因Lin28A、OCT4、SOX2表达下调。此外,BVDV感染可诱导ssc铁下垂。此外,CRISPR-Cas9介导的山羊ssc中CD46的编辑导致BVDV感染率下降,减轻了病毒对细胞存活和增殖的负面影响。本研究为研究BVDV感染雄性家畜生殖功能下降的机制提供了新的思路,为制定针对性的抗病育种策略奠定了基础。
{"title":"CRISPR/Cas9-generated CD46-knockout spermatogonial stem cells reveal mechanisms of BVDV-induced reproductive dysfunction in male livestock","authors":"Jiannan Li ,&nbsp;Xueting Li ,&nbsp;Xiao Li ,&nbsp;Wenjie Xu ,&nbsp;Liming Yuan ,&nbsp;Hongzhao Shi ,&nbsp;Zuo Lei ,&nbsp;Na Li ,&nbsp;Yulei Wei ,&nbsp;Jinlian Hua","doi":"10.1016/j.vetmic.2025.110807","DOIUrl":"10.1016/j.vetmic.2025.110807","url":null,"abstract":"<div><div>Bovine viral diarrhea virus (BVDV) is a major viral pathogen that affects ruminants, resulting in significant economic losses due to issues such as immunosuppression, reproductive disorders, and growth retardation. Bulls infected with this virus may become infertile within a few months and can transmit the virus to susceptible cattle during mating. However, the mechanism of BVDV impairing the reproductive function of male livestock is not clear, as there is no suitable cell model. This study used spermatogonial stem cells(SSCs) from cattle and goats as research materials to explore the mechanism by which BVDV affects the reproductive function of male livestock. The results of this study indicate that both cytopathic (cp) and noncytopathic (ncp) BVDV can replicate in SSCs and that SSCs are capable of producing infectious BVDV. Giemsa staining showed significant changes in the morphology of SSCs after BVDV infection. Western blot and mRNA analysis showed that proliferation-related genes (<em>PCNA</em>, <em>CCND1</em>, <em>CDK2</em>) and SSC functional genes (<em>Lin28A</em>, <em>OCT4</em>, <em>SOX2</em>) were down regulated after infection. In addition, BVDV infection can induce ferroptosis in SSCs. Furthermore, CRISPR-Cas9 mediated editing of CD46 in goat SSCs resulted in a decrease in BVDV infection rate and alleviated the negative impact of the virus on cell survival and proliferation. This study provides new insights into the mechanism of reduced reproductive function in male livestock infected with BVDV, and lays the foundation for developing targeted disease resistant breeding strategies.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"312 ","pages":"Article 110807"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145570253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NA-N322S and G389D mutations synergize with PB2-627K to enhance H7N9 pathogenicity in mammals NA-N322S和G389D突变与PB2-627K协同增强H7N9在哺乳动物中的致病性
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-30 DOI: 10.1016/j.vetmic.2025.110775
Huafen Zheng , Yufan Chen , Ruyi Gao , Wenhao Yang , Xiaolong Lu , Yu Chen , Min Gu , Jiao Hu , Xiaowen Liu , Shunlin Hu , Kaituo Liu , Xiaoquan Wang , Xiufan Liu
The H7N9 subtype avian influenza virus (AIV) is currently the subtype with the highest number of human infection cases, with a mortality rate of nearly 40 %,40 %, posing a serious threat to public health. We have previously reported that two avian H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit distinct pathogenicity in mice, in which the polymerase proteins cooperatively increased pathogenicity in mice. Still, the enhancement did not reach the level of JTC11. To further investigate the genetic basis of the virulence difference, we constructed a series of mutant viruses using reverse genetics. We found that the combination of NA-N322S or NA-G389D mutations with PB2-E627K was not sufficient to increase the pathogenicity of H7N9 in mice, although it was able to enhance the neuraminidase activity of the virus. However, the NA-N322S and NA-G389D mutations combined with PB2-E627K significantly enhanced H7N9 pathogenicity. In addition, these combined mutations enhanced neuraminidase enzyme activity, thereby enhancing viral replication, inflammatory cytokine expression, and lung damage, ultimately increasing pathogenicity in mice. In conclusion, this study reveals that the virulence in H7N9 is a polygenic trait and identifies new virulence-associated residues (NAN322S+G389D combined with PB2-E627K). These findings not only enhance our comprehension of the molecular mechanisms underlying AIVs pathogenicity in mammals, but also provide early warning information for preventing cross-species transmission of the H7N9 virus and for potential future pandemics.
H7N9亚型禽流感病毒(AIV)是目前人类感染病例数量最多的亚型,死亡率近40%,40 %,对公众健康构成严重威胁。我们之前报道了两株H7N9禽流感分离株(A/chicken/Eastern China/JTC4/2013和A/chicken/Eastern China/JTC11/2013)在小鼠中表现出不同的致病性,其中聚合酶蛋白协同提高了小鼠的致病性。但是,这种增强并没有达到JTC11的水平。为了进一步研究毒力差异的遗传基础,我们利用反向遗传学构建了一系列突变病毒。我们发现,NA-N322S或NA-G389D突变与PB2-E627K结合,虽然能够增强病毒的神经氨酸酶活性,但不足以增加H7N9在小鼠中的致病性。然而,NA-N322S和NA-G389D突变与PB2-E627K联合显著增强了H7N9的致病性。此外,这些组合突变增强了神经氨酸酶活性,从而增强了病毒复制、炎症细胞因子表达和肺损伤,最终增加了小鼠的致病性。综上所述,本研究揭示了H7N9的毒力是一种多基因特征,并鉴定出新的毒力相关残基(NAN322S+G389D联合PB2-E627K)。这些发现不仅加深了我们对aiv在哺乳动物中致病性的分子机制的理解,而且为预防H7N9病毒的跨物种传播和潜在的未来大流行提供了早期预警信息。
{"title":"NA-N322S and G389D mutations synergize with PB2-627K to enhance H7N9 pathogenicity in mammals","authors":"Huafen Zheng ,&nbsp;Yufan Chen ,&nbsp;Ruyi Gao ,&nbsp;Wenhao Yang ,&nbsp;Xiaolong Lu ,&nbsp;Yu Chen ,&nbsp;Min Gu ,&nbsp;Jiao Hu ,&nbsp;Xiaowen Liu ,&nbsp;Shunlin Hu ,&nbsp;Kaituo Liu ,&nbsp;Xiaoquan Wang ,&nbsp;Xiufan Liu","doi":"10.1016/j.vetmic.2025.110775","DOIUrl":"10.1016/j.vetmic.2025.110775","url":null,"abstract":"<div><div>The H7N9 subtype avian influenza virus (AIV) is currently the subtype with the highest number of human infection cases, with a mortality rate of nearly 40 %,40 %, posing a serious threat to public health. We have previously reported that two avian H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit distinct pathogenicity in mice, in which the polymerase proteins cooperatively increased pathogenicity in mice. Still, the enhancement did not reach the level of JTC11. To further investigate the genetic basis of the virulence difference, we constructed a series of mutant viruses using reverse genetics. We found that the combination of NA-N322S or NA-G389D mutations with PB2-E627K was not sufficient to increase the pathogenicity of H7N9 in mice, although it was able to enhance the neuraminidase activity of the virus. However, the NA-N322S and NA-G389D mutations combined with PB2-E627K significantly enhanced H7N9 pathogenicity. In addition, these combined mutations enhanced neuraminidase enzyme activity, thereby enhancing viral replication, inflammatory cytokine expression, and lung damage, ultimately increasing pathogenicity in mice. In conclusion, this study reveals that the virulence in H7N9 is a polygenic trait and identifies new virulence-associated residues (NA<sup>N322S+G389D</sup> combined with PB2-E627K). These findings not only enhance our comprehension of the molecular mechanisms underlying AIVs pathogenicity in mammals, but also provide early warning information for preventing cross-species transmission of the H7N9 virus and for potential future pandemics.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"312 ","pages":"Article 110775"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DDX21 nuclear-cytoplasmic shuttling recruits RPS18 to viral dsRNA to promote CSFV replication DDX21核细胞质穿梭招募RPS18进入病毒dsRNA,促进猪瘟病毒复制。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-29 DOI: 10.1016/j.vetmic.2025.110822
Bingke Li , Bolun Zhou , Chenchen Sun , Shurou Li , Ye Bai , Ruibo Zhao , Yiwan Song , Yintao He , Lin Yi , Hongxing Ding , Shuangqi Fan , Jinding Chen , Keke Wu
Cellular pathogens exploit host machinery by forcibly relocalizing and repurposing nuclear proteins. Here, we reveal that Classic Swine Fever Virus (CSFV) hijacks DEAD-box helicase 21 (DDX21),dynamically translocating it from nucleus to cytoplasm and converts it into a non-enzymatic scaffold that recruits ribosomal protein S18 (RPS18) onto viral double-stranded RNA (dsRNA). This virus-induced DDX21-RPS18 axis creates a self-amplifying loop: DDX21 upregulates RPS18 via its helicase domain, while RPS18 suppresses DDX21 levels. Crucially, RPS18 dose-dependently enhances viral NS4A protein synthesis, with DDX21’s pro-viral activity being strictly RPS18-dependent. By orchestrating RPS18-dsRNA binding independent of its helicase activity, cytoplasmic DDX21 spatially co-opts ribosomal components to selectively drive viral protein translation. Our findings reveal a mechanism in which CSFV-triggered relocalization of DDX21 enables viral hijacking of host translation, illustrating how spatial control of RNA-binding proteins can be exploited to redirect cellular functions for pathogen replication.
细胞病原体利用宿主机制强行重新定位和重新利用核蛋白。本研究揭示了经典猪瘟病毒(CSFV)劫持DEAD-box解旋酶21 (DDX21),动态地将其从细胞核转移到细胞质,并将其转化为非酶支架,将核糖体蛋白S18 (RPS18)募集到病毒双链RNA (dsRNA)上。这种病毒诱导的DDX21-RPS18轴产生了一个自我扩增的环:DDX21通过其解旋酶结构域上调RPS18,而RPS18抑制DDX21的水平。关键是,RPS18剂量依赖性地增强病毒NS4A蛋白合成,DDX21的前病毒活性严格依赖于RPS18。通过协调RPS18-dsRNA独立于解旋酶活性的结合,细胞质DDX21在空间上选择核糖体成分来选择性地驱动病毒蛋白翻译。我们的研究结果揭示了csfv引发的DDX21重定位使病毒劫持宿主翻译的机制,说明了如何利用rna结合蛋白的空间控制来重定向病原体复制的细胞功能。
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Veterinary microbiology
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