Veterinary microbiology最新文献_第7页

Beyond macrophages: FIPV tropism includes T and B lymphocytes 除巨噬细胞外：趋向性FIPV包括T和B淋巴细胞。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-31 DOI: 10.1016/j.vetmic.2025.110864

Aadhavan Balakumar , Patrawin Wanakumjorn , Kazuto Kimura , Ehren McLarty , Katherine Farrell , Terza Brostoff , Jully Pires , Tamar Cohen-Davidyan , Jennifer M. Cassano , Brian Murphy , Krystle Reagan , Amir Kol

If untreated, feline infectious peritonitis (FIP) is a fatal disease that is caused by feline infectious peritonitis virus (FIPV), a virulent biotype of feline coronavirus (FCoV) that disseminates broadly and triggers severe systemic inflammation. While the prevailing model holds that FIPV selectively infects monocytes/macrophages, the full range of susceptible cell types and the mechanisms of immune cell invasion remain poorly defined. Here, we applied single-cell RNA sequencing, multiplex immunofluorescence, and in situ hybridization to mesenteric lymph node aspirates and formalin fixed and paraffin embedded lymph node tissues from cats with naturally occurring effusive FIP. We identified FIPV RNA and nucleocapsid protein in T and B lymphocytes and myeloid cells, and subgenomic viral RNA in T cells, demonstrating cell entry and viral genomic replication across multiple immune compartments. Rare FIPV RNA–positive lymphocytes persisted after antiviral treatment cessation and resolution of clinical signs. These findings revise current models of FIPV pathogenesis and reveal new insights into coronavirus-driven immune dysregulation, viral persistence, and relapse. Our study highlights the utility of FIP as a naturally occurring animal model for exploring adaptive immune cell infection in coronavirus diseases, providing a translational platform for understanding virus–host interactions that drive chronic or relapsing immunopathology.

如果不及时治疗，猫传染性腹膜炎（FIP）是一种由猫传染性腹膜炎病毒（FIPV）引起的致命疾病，FIPV是一种毒力强的猫冠状病毒（FCoV），可广泛传播并引发严重的全身炎症。虽然流行的模型认为FIPV选择性地感染单核/巨噬细胞，但各种易感细胞类型和免疫细胞入侵机制仍然不明确。在这里，我们将单细胞RNA测序、多重免疫荧光和原位杂交应用于自然发生的渗出性FIP猫的肠系膜淋巴结抽吸物和福尔马林固定和石蜡包埋的淋巴结组织。我们在T淋巴细胞、B淋巴细胞和髓细胞中鉴定了FIPV RNA和核衣壳蛋白，在T细胞中鉴定了亚基因组病毒RNA，证明了细胞进入和病毒基因组复制跨越多个免疫区室。罕见的FIPV rna阳性淋巴细胞在抗病毒治疗停止和临床症状消退后仍然存在。这些发现修订了目前关于FIPV发病机制的模型，并揭示了冠状病毒驱动的免疫失调、病毒持续存在和复发的新见解。我们的研究强调了FIP作为一种自然发生的动物模型的效用，用于探索冠状病毒疾病中的适应性免疫细胞感染，为理解驱动慢性或复发性免疫病理的病毒-宿主相互作用提供了一个翻译平台。

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引用次数: 0

NSP9 is a key virulence determinant in highly pathogenic PRRSV-mediated thymic injury via synergistic activation of apoptotic and metabolic pathways 在高致病性prrsv介导的胸腺损伤中，NSP9是一个关键的毒力决定因素，通过凋亡和代谢途径的协同激活。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-31 DOI: 10.1016/j.vetmic.2025.110868

Fanliang Meng , Chenchen Cui , Xinyi Huang , Qianru Zhang , Longshuai Yao , Xuehui Cai , Tongqing An , Gang Wang

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) induces severe thymic atrophy, contributing to immunosuppression in infected piglets. This study investigated the roles of viral nonstructural proteins NSP9 and NSP10 in thymic pathogenesis using chimeric viruses (HC9 and HC10) generated by replacing NSP9/NSP10 of the HP-PRRSV HuN4 strain with those from the classical CH-1a strain. In vitro replication was significantly affected by these swaps, with NSP9 showing a more pronounced effect. In vivo replication kinetics, pathogenicity, and thymus damage were analyzed in piglets inoculated with the HuN4 strain or the chimeric strains. The study found that NSP9 and NSP10 are closely associated with PRRSV replication efficiency and pathogenicity, with NSP9 having a greater impact on thymus atrophy and both NSP9 and NSP10 playing a key role in inducing thymocytes apoptosis. Transcriptomic analysis revealed that HuN4 infection significantly upregulated genes associated with apoptosis, inflammatory responses, and metabolic pathways (e.g., NF-κB, PI3K-Akt, and p53 signaling), while HC9 showed attenuated effects. Flow cytometry confirmed HuN4-induced depletion of CD4⁺CD8⁺ thymocytes and dysregulated surface marker expression (CD4). TUNEL assays and apoptosis-related gene profiling further implicated NSP9 in activating both intrinsic and extrinsic apoptotic pathways. Notably, metabolic pathway enrichment suggested crosstalk between apoptosis and energy sensing (e.g., AMPK-mTOR). These findings highlight NSP9 as a critical virulence factor driving thymic atrophy through synergistic immune hyperactivation, apoptotic cascades, and metabolic reprogramming, providing novel insights for PRRSV vaccine design and immunomodulatory strategies.

高致病性猪繁殖与呼吸综合征病毒（HP-PRRSV）引起仔猪严重胸腺萎缩，导致仔猪免疫抑制。本研究利用HC9和HC10嵌合病毒将HP-PRRSV HuN4株的NSP9/NSP10替换为经典CH-1a株的NSP9/NSP10，研究了病毒非结构蛋白NSP9和NSP10在胸腺发病中的作用。这些交换显著影响了体外复制，其中NSP9表现出更明显的影响。研究了HuN4株和嵌合株接种仔猪的体内复制动力学、致病性和胸腺损伤情况。研究发现，NSP9和NSP10与PRRSV的复制效率和致病性密切相关，其中NSP9对胸腺萎缩的影响更大，NSP9和NSP10在诱导胸腺细胞凋亡中都起着关键作用。转录组学分析显示，HuN4感染显著上调了与凋亡、炎症反应和代谢途径相关的基因（如NF-κB、PI3K-Akt和p53信号传导），而HC9的作用减弱。流式细胞术证实了hun4诱导的CD4+CD8+胸腺细胞耗竭和表面标记物表达失调（CD4）。TUNEL实验和凋亡相关基因谱进一步表明，NSP9在激活内源性和外源性凋亡通路中都有作用。值得注意的是，代谢途径的富集表明细胞凋亡和能量感应（如AMPK-mTOR）之间存在串扰。这些发现强调了NSP9是通过协同免疫超激活、凋亡级联和代谢重编程驱动胸腺萎缩的关键毒力因子，为PRRSV疫苗设计和免疫调节策略提供了新的见解。

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引用次数: 0

ANXA2 stabilizes mTOR at the plasma membrane to facilitate autophagic flux for CSFV release ANXA2稳定质膜上的mTOR，促进CSFV释放的自噬通量

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-31 DOI: 10.1016/j.vetmic.2025.110863

Tao Wang , Liangcai Da , Junfang Zhao , Hong Yuan , Ying Sun , Liang Zhang , Kun Li , Jing Zhang , Pu Sun , Zhixun Zhao , Qiang Zhang , Yuanji Zhang , Yebing Liu , Xingwen Bai , Zengjun Lu

Classical swine fever virus (CSFV), a member of the Flaviviridae family, remains a major pathogen responsible for substantial economic losses in the global swine industry. Autophagy plays a critical role in the life cycle and virulence of CSFV, however, the mechanisms through which the virus regulates autophagy are still not fully understood. In this study, we identified ANXA2, a calcium-dependent phospholipid-binding protein, within autophagy-derived vesicles that facilitate CSFV transmission. We demonstrated that ANXA2 modulates CSFV release in a manner dependent on autophagy. Moreover, multiple lines of evidence, including Western blot, LC3 puncta formation, tandem fluorescence assay, and electron microscopy, consistently showed that ANXA2 promotes CSFV-induced autophagy. Mechanistically, ANXA2 overexpression reduced mTOR phosphorylation, while its knockout increased phosphorylation. Comprehensive binding assays revealed that both ANXA2 and the CSFV envelope protein E2 interact with mTOR with high affinity. Domain mapping further indicated that ANXA2 and E2 bind to distinct regions of mTOR, suggesting a synergistic mechanism for autophagy activation. Confocal microscopy showed that ANXA2 facilitates mTOR accumulation at the plasma membrane during infection. Importantly, relocalizing ANXA2 to mitochondria attenuated CSFV-induced autophagy. Collectively, these results indicate that ANXA2 modulates CSFV-triggered autophagy by controlling mTOR subcellular localization, thereby influencing viral production. This study unveils a novel strategy by which CSFV co-opts the ANXA2–mTOR axis to manipulate autophagic processes, highlighting potential targets for future antiviral interventions.

经典猪瘟病毒（CSFV）是黄病毒科的一员，仍然是造成全球养猪业重大经济损失的主要病原体。自噬在猪瘟病毒的生命周期和毒力中起着至关重要的作用，然而，病毒调控自噬的机制尚不完全清楚。在这项研究中，我们在自噬衍生的囊泡中发现了ANXA2，一种钙依赖性磷脂结合蛋白，可促进猪瘟病毒的传播。我们证明了ANXA2以依赖于自噬的方式调节猪瘟病毒的释放。此外，包括Western blot、LC3斑点形成、串联荧光实验和电镜在内的多种证据一致表明，ANXA2促进了csfv诱导的自噬。机制上，ANXA2过表达降低了mTOR的磷酸化，而敲除则增加了磷酸化。综合结合实验显示，ANXA2和CSFV包膜蛋白E2都与mTOR有高亲和力的相互作用。结构域定位进一步表明，ANXA2和E2结合到mTOR的不同区域，提示自噬激活的协同机制。共聚焦显微镜显示，在感染过程中，ANXA2促进了mTOR在质膜上的积累。重要的是，将ANXA2重新定位到线粒体可以减弱猪瘟病毒诱导的自噬。综上所述，这些结果表明ANXA2通过控制mTOR亚细胞定位来调节猪瘟引发的自噬，从而影响病毒的产生。这项研究揭示了CSFV利用ANXA2-mTOR轴操纵自噬过程的一种新策略，突出了未来抗病毒干预的潜在靶点。

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引用次数: 0

ENTR1 stabilizes MAVS by inhibiting NIX-mediated mitophagy to restrict BPIV3 and VSV replication ENTR1通过抑制nix介导的线粒体自噬来抑制BPIV3和VSV的复制，从而稳定MAVS。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-31 DOI: 10.1016/j.vetmic.2025.110865

Xiaoyang Yao , Xingyu Li , Lixiang Shi, Hongmei Wang, Hongbin He

Endosome-associated trafficking regulator 1 (ENTR1) is implicated in cell apoptosis, cytokinesis, and adipogenesis, but its role in antiviral innate immunity has not been elucidated. In this study, we identify ENTR1 as a positive regulatory factor for type I interferon (IFN-I) signaling pathway, which suppresses bovine parainfluenza virus type 3 (BPIV3) and vesicular stomatitis virus (VSV) replication. Further investigations revealed that ENTR1 deficiency enhanced Nip3-like protein X (NIX)-mediated mitophagy, leading to accelerated degradation of mitochondrial antiviral signaling protein (MAVS) during viral infection. Mechanistically, ENTR1 knockout resulted in increased accumulation of NIX on mitochondria, which promoted the autophagic degradation of MAVS. Importantly, silencing NIX rescued MAVS protein levels and significantly reduced viral titers in ENTR1-deficient cells. Moreover, NIX silencing prevented the degradation of MAVS and consequently reduced viral titers in ENTR1-deficient cells. Consequently, our findings reveal a novel regulatory axis in which ENTR1 stabilizes MAVS by suppressing NIX-dependent mitophagy, thereby enhancing antiviral IFN-I responses. This study not only uncovers a previously unrecognized function of ENTR1 in antiviral immunity but also identifies ENTR1 as a potential target for developing broad-spectrum antiviral therapeutics against RNA viruses.

内核体相关运输调节因子1 （ENTR1）与细胞凋亡、细胞分裂和脂肪形成有关，但其在抗病毒先天免疫中的作用尚未阐明。在这项研究中，我们发现ENTR1是I型干扰素（IFN-I）信号通路的正调控因子，该信号通路抑制牛副流感病毒3型（BPIV3）和水疱性口炎病毒（VSV）的复制。进一步的研究表明，ENTR1缺陷增强了nip3样蛋白X （NIX）介导的线粒体自噬，导致病毒感染期间线粒体抗病毒信号蛋白（MAVS）的降解加速。机制上，ENTR1敲除导致线粒体上NIX的积累增加，从而促进MAVS的自噬降解。重要的是，沉默NIX可挽救MAVS蛋白水平，并显著降低entr1缺陷细胞中的病毒滴度。此外，NIX沉默阻止了MAVS的降解，从而降低了entr1缺陷细胞中的病毒滴度。因此，我们的研究结果揭示了一个新的调控轴，其中ENTR1通过抑制nix依赖性的有丝分裂来稳定MAVS，从而增强抗病毒IFN-I反应。这项研究不仅揭示了ENTR1在抗病毒免疫中的一个以前未被认识到的功能，而且还确定了ENTR1作为开发针对RNA病毒的广谱抗病毒治疗的潜在靶点。

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引用次数: 0

Pathogenicity of Porcine reproductive and respiratory syndrome virus in the reproductive system of female piglets: Pathological damage to the uterine horns and developmental arrest 猪生殖与呼吸综合征病毒在母猪生殖系统中的致病性：子宫角的病理性损伤和发育停滞。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-30 DOI: 10.1016/j.vetmic.2025.110867

Yi-Xin Yan , Ying Guan , Lei Zhao , Han-Yu Li , Tong Xu , Li-Na Shao , Si-Yuan Lai , Yi Qing , Liang-Peng Ge , Zuo-Hua Liu , Jing Sun , Xiu Zeng , Ling Zhu , Zhi-Wen Xu

Porcine reproductive and respiratory syndrome virus (PRRSV) infection in pig herds is the primary cause of reproductive disorders in sows, posing a significant threat to the global swine industry. The infection directly impairs reproductive efficiency in sows. However, the effects of PRRSV on the reproductive system of female piglets have not been thoroughly investigated. In this study, female piglets were infected with PRRSV, and the extent of damage to the reproductive system was systematically evaluated. Following PRRSV infection, damage was observed in oocytes, luminal epithelium (LE), glandular epithelium (GE), and stromal (S) cells of the uterus, accompanied by arrested development of glands and vasculature in the uterine horns. Immunohistochemical analysis (IHC) demonstrated the localization of viral antigens within the endometrial epithelial cells of the uterine horns. PRRSV infection suppressed the expression of estrogen receptor α (ESR-α) in the uterine horns. Interestingly, the proliferation capacity of endometrial cells in the uterine horns was simultaneously reduced, and multiple genes and pathways regulating cell proliferation were also downregulated. Disruption of tight junctions (TJ) at the uterine horns further indicated compromised epithelial barrier integrity. This barrier disruption was accompanied by the initiation of a cytokine storm and enrichment of inflammation-related pathways (NF-κB, chemokine, Toll-like receptor, TNF, and JAK-STAT signaling), indicating substantial inflammatory injury consistent with viral pathology. These results demonstrate that PRRSV inflicts severe damage on the ovaries and uterus of female piglets, thereby threatening the healthy development of the sow reproductive system.

猪繁殖与呼吸综合征病毒（PRRSV）在猪群中的感染是母猪繁殖障碍的主要原因，对全球养猪业构成重大威胁。这种感染直接损害母猪的繁殖效率。然而，PRRSV对母猪生殖系统的影响尚未得到深入的研究。本研究用PRRSV感染母猪，系统评价其对生殖系统的损害程度。PRRSV感染后，观察到子宫卵母细胞、腔上皮（LE）、腺上皮（GE）和基质细胞(S)受损，并伴有子宫角腺体和脉管系统发育受阻。免疫组化分析（IHC）证实病毒抗原定位于子宫角的子宫内膜上皮细胞内。PRRSV感染可抑制子宫角雌激素受体α (ESR-α)的表达。有趣的是，子宫角内子宫内膜细胞的增殖能力同时降低，调节细胞增殖的多种基因和途径也下调。子宫角紧密连接（TJ）的破坏进一步表明上皮屏障完整性受损。这种屏障破坏伴随着细胞因子风暴的启动和炎症相关通路（NF-κB、趋化因子、toll样受体、TNF和JAK-STAT信号）的富集，表明存在与病毒病理一致的实质性炎症损伤。上述结果表明，PRRSV对母猪卵巢和子宫造成严重损害，威胁母猪生殖系统的健康发育。

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引用次数: 0

Identification of porcine-derived atypical intestinal pathogenic Escherichia coli reveals to a hidden threat of extraintestinal infection 猪源非典型肠道致病性大肠杆菌的鉴定揭示了肠外感染的潜在威胁

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-30 DOI: 10.1016/j.vetmic.2025.110860

Zhonghao Chen , Simin Lv , Shiyu Zhang , Yong Yu , Jiale Ma , Huochun Yao , Xinming Pan

Post-weaning diarrhea in piglets is primarily caused by enterotoxigenic Escherichia coli (ETEC) and Shiga toxin-producing E. coli (STEC). However, the diversity and combinations of virulence factors among clinical porcine isolates remain incompletely characterized. Here, we systematically screened 296 E. coli isolates from diarrheic piglets and identified nine isolates (3.0 %) that lacked classical ETEC/STEC virulence factors but co-harbored F18 fimbriae and a hemolysin gene cluster. These F18⁺&hly⁺ strains exhibited strong intestinal adhesion and colonization in vitro and in vivo and were designated enteroadherent hemolytic E. coli (EAHEC). Notably, EAHEC strains belonging to phylogroup D also displayed extraintestinal pathogenicity in mouse models, indicating cross-niche potential. Based on this finding, we identified 17 hybrid pathogenic E. coli (HyPEC) isolates (5.7 %) by PCR screening. These hybrid strains were classified based on two criteria: (i) the presence of both intestinal virulence markers (ETEC/EPEC/STEC/EAHEC) and ExPEC/UPEC-associated virulence genes, or (ii) the carriage of ExPEC/UPEC-associated virulence genes despite lacking classical intestinal pathotype markers, while nonetheless exhibiting intestinal pathogenic phenotypes. Phenotypic assays showed that most HyPEC strains retained strong intestinal colonization capacity, whereas systemic infection capacity varied by phylogroup, with B2 and D lineages exhibiting the highest virulence. Overall, our study documents the existence and virulence potential of atypical enteroadherent hemolytic and hybrid E. coli in pigs, highlights diverse virulence-module combinations in porcine isolates, and indicates that recognition of such atypical/hybrid strains may have implications for future diagnostics and surveillance of porcine diarrheal disease.

仔猪断奶后腹泻主要由产肠毒素大肠杆菌（ETEC）和产志贺毒素大肠杆菌（STEC）引起。然而，临床猪分离株中毒力因子的多样性和组合仍然不完全确定。在这里，我们系统地筛选了296株来自腹泻仔猪的大肠杆菌，并鉴定出9株（3.0 %）缺乏经典的ETEC/STEC毒力因子，但同时携带F18菌膜和溶血素基因群。这些F18 + & hly +菌株在体外和体内均表现出较强的肠道粘附性和定植性，被命名为肠黏附溶血性大肠杆菌（EAHEC）。值得注意的是，属于D系的EAHEC菌株在小鼠模型中也表现出肠外致病性，这表明了跨生态位的潜力。基于这一发现，我们通过PCR筛选鉴定出17株杂交致病性大肠杆菌（HyPEC）（5.7% %）。这些杂交菌株根据两个标准进行分类：(i)肠道毒力标记（ETEC/EPEC/STEC/EAHEC）和ExPEC/ upec相关毒力基因的存在，或（ii）携带ExPEC/ upec相关毒力基因，尽管缺乏经典的肠道病理标记，但仍表现出肠道致病表型。表型分析表明，大多数HyPEC菌株具有较强的肠道定植能力，而系统感染能力因系群而异，B2和D系表现出最高的毒力。总的来说，我们的研究记录了猪中非典型肠黏附溶血性大肠杆菌和杂交大肠杆菌的存在和毒力潜力，强调了猪分离株中不同的毒力模块组合，并表明识别这种非典型/杂交菌株可能对未来猪腹泻病的诊断和监测具有重要意义。

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引用次数: 0

Functional characterisation of metabolism-related genes required for the survival of Mycoplasma bovis in association with host cells 与宿主细胞相关的牛支原体存活所需的代谢相关基因的功能特征

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-30 DOI: 10.1016/j.vetmic.2025.110861

Shijie Geng , Sheik Nadeem Elahee Doomun , Jordi Hondrogiannis , David P. De Souza , Anna Kanci Condello , Glenn F. Browning , Sara M. Klose , Kelly A. Tivendale , Nadeeka K. Wawegama

Metabolic functions of mycoplasmas play an important role in their interactions with their host. Recent studies examining the capacity of mutants of Mycoplasma bovis to survive in co-culture with Madin-Darby bovine kidney (MDBK) cells have identified three genes, MBOVPG45_0728, MBOVPG45_0028 and MBOVPG45_0327, that are essential for the survival of M. bovis in association with host cells. In the study described here, the metabolic profiles of the mutant strains with transposons inserted into these genes (∆MBOVPG45_0728, ∆MBOVPG45_0028 and ∆MBOVPG45_0327) were compared with that of the parent strain, PG45, to investigate the metabolic functions of the proteins. Steady-state metabolomic analysis did not identify significant alterations in metabolites associated with glucose metabolism in the ∆MBOVPG45_0728 mutant, suggesting that the product of MBOVPG45_0728 does not have the role in phosphoglucomutase activity predicted by bioinformatic analysis, and may play a role in amino acid and lipid metabolism. Metabolomic footprinting analyses detected significant differences in changes in medium components in cultures of ∆MBOVPG45_0028 and ∆MBOVPG45_0327 compared to PG45. These results were consistent with bioinformatic predictions that these two genes encoded components of transporter systems, and suggested that the protein encoded by the MBOVPG45_0028 gene is involved in nucleoside uptake, and that encoded by the MBOVPG45_0327 gene is involved in the efflux of organic acids. Overall, comparative metabolomic profiling revealed metabolic functions of M. bovis that are critical in interactions with host cells, furthering our understanding of metabolic mechanisms required for successful infection with M. bovis.

支原体的代谢功能在其与宿主的相互作用中起着重要作用。最近的研究检测了牛支原体突变体与Madin-Darby牛肾（MDBK）细胞共培养的存活能力，发现了MBOVPG45_0728、MBOVPG45_0028和MBOVPG45_0327三个基因，它们对牛支原体与宿主细胞联合存活至关重要。在本研究中，将转座子插入这些基因的突变菌株（∆MBOVPG45_0728，∆MBOVPG45_0028和∆MBOVPG45_0327）与亲本菌株PG45的代谢谱进行比较，以研究这些蛋白质的代谢功能。稳态代谢组学分析未发现∆MBOVPG45_0728突变体中与葡萄糖代谢相关的代谢物发生显著变化，这表明MBOVPG45_0728的产物不具有生物信息学分析预测的磷酸化葡萄糖糖化酶活性的作用，而可能在氨基酸和脂质代谢中发挥作用。代谢组学足迹分析发现，与PG45相比，∆MBOVPG45_0028和∆MBOVPG45_0327培养物中培养基成分的变化存在显著差异。这些结果与生物信息学预测一致，即这两个基因编码转运系统组分，并提示MBOVPG45_0028基因编码的蛋白质参与核苷摄取，MBOVPG45_0327基因编码的蛋白质参与有机酸的外排。总的来说，比较代谢组学分析揭示了牛分枝杆菌的代谢功能，这在与宿主细胞的相互作用中是至关重要的，进一步加深了我们对牛分枝杆菌成功感染所需的代谢机制的理解。

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引用次数: 0

SERPINB1 promotes porcine deltacoronavirus replication by targeting the viral accessory protein NS7a SERPINB1通过靶向病毒附属蛋白NS7a促进猪三角冠状病毒复制

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-30 DOI: 10.1016/j.vetmic.2025.110869

Junfang Yan , Xinru Liu , Huixin Zhu , Liang Li , Hongye Pan , Renjie Bao , Qiutian Li , Jing Sun , Houhui Song , Mingjun Su

Porcine deltacoronavirus (PDCoV) is an emerging porcine enteric coronavirus in China, with the risk of cross-species transmission and zoonotic infection. SERPINB1, serine protease inhibitor, is a potential therapeutic target. It is unclear whether its role in PDCoV replication. Our study found that PDCoV infection upregulates the expression level of SERPINB1, suggesting a potential role for SERPINB1 in the viral life cycle. Further investigation revealed that SERPINB1 is an essential factor for viral replication, and its RCL domain is the key region for its viral-promoting activity. Moreover, SERPINB1 interacts with accessory protein NS7a of PDCoV. Understanding the mechanism by which SERPINB1 targets viral encoded proteins to promote PDCoV replication can enrich the pathogenesis and immune mechanism of PDCoV, and provide new targets and important theoretical basis for the development of antiviral drugs.

猪三角冠状病毒（PDCoV）是中国一种新型猪肠道冠状病毒，具有跨种传播和人畜共患感染的风险。丝氨酸蛋白酶抑制剂SERPINB1是一个潜在的治疗靶点。目前尚不清楚它是否在PDCoV复制中起作用。我们的研究发现，PDCoV感染上调了SERPINB1的表达水平，提示SERPINB1在病毒生命周期中可能发挥作用。进一步研究发现，SERPINB1是病毒复制的重要因子，其RCL结构域是其促病毒活性的关键区域。此外，SERPINB1与PDCoV的附属蛋白NS7a相互作用。了解SERPINB1靶向病毒编码蛋白促进PDCoV复制的机制，可以丰富PDCoV的发病机制和免疫机制，为抗病毒药物的开发提供新的靶点和重要的理论依据。

引用次数: 0

AS-IV exhibits anti-SADS-CoV effects through the inhibition of the MAPK/JNK signaling pathway mediated by the S1 protein AS-IV通过抑制S1蛋白介导的MAPK/JNK信号通路表现出抗sads - cov的作用

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-29 DOI: 10.1016/j.vetmic.2025.110858

Shuiping Liu, Yuting Zeng, Dengju Guo, Jinwei Huang, Xi Li, Guihong Zhang

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a porcine intestinal alpha coronavirus that infects newborn piglets. Clinical symptoms include acute diarrhea, vomiting, dehydration, and death. There is no effective prevention and control vaccine yet, so new measures are urgently needed, including antiviral strategies. Astragaloside IV (AS-IV) has several pharmacological properties, including immunomodulatory, anti-inflammatory, and antiviral effects. This research found that AS-IV inhibited SADS-CoV replication in vitro through antagonizing the MAPK/JNK pathway mediated by SADS-CoV S1 protein and reducing apoptosis. In addition, SADS-CoV S1 protein interacted with RPSA to activate MAPK/JNK pathway to facilitate virus replication. AS-IV reduced the clinical symptoms and intestinal pathological damage caused by SADS-CoV infection. AS-IV significantly reduced the viral loads in the intestinal tissue and anal swabs, and increased survival of infected piglets, suggesting that AS-IV is a potential antiviral drug for the prevention and control of SADS-CoV. Additionally, in vitro and in vivo experiments showed that AS-IV downregulated the levels of inflammatory factors, including IL-1β, IL-6, IL-8 and TNF-α, indicating that AS-IV ameliorated SADS-CoV infection-induced inflammatory response. In conclusion AS-IV exerts antiviral effects and anti-inflammatory responses through inhibiting the MAPK/JNK signaling pathway mediated by SADS-CoV S1. This study provides a theoretical basis for the research and development of anti-SADS-CoV drugs.

猪急性腹泻综合征冠状病毒（SADS-CoV）是一种感染新生仔猪的猪肠道α冠状病毒。临床症状包括急性腹泻、呕吐、脱水和死亡。目前还没有有效的预防和控制疫苗，因此迫切需要采取新的措施，包括抗病毒策略。黄芪甲苷（AS-IV）具有多种药理特性，包括免疫调节、抗炎和抗病毒作用。本研究发现，AS-IV通过拮抗SADS-CoV S1蛋白介导的MAPK/JNK通路，减少细胞凋亡，抑制SADS-CoV体外复制。此外，SADS-CoV S1蛋白与RPSA相互作用，激活MAPK/JNK通路，促进病毒复制。AS-IV减轻了SADS-CoV感染引起的临床症状和肠道病理损害。AS-IV显著降低了感染仔猪肠道组织和肛门拭子的病毒载量，提高了感染仔猪的存活率，提示AS-IV是一种潜在的抗病毒药物，可用于预防和控制SADS-CoV。此外，体外和体内实验表明，AS-IV下调炎症因子IL-1β、IL-6、IL-8和TNF-α水平，表明AS-IV改善了SADS-CoV感染诱导的炎症反应。综上所述，AS-IV通过抑制SADS-CoV S1介导的MAPK/JNK信号通路发挥抗病毒和抗炎作用。本研究为抗sads - cov药物的研发提供了理论依据。

{"title":"AS-IV exhibits anti-SADS-CoV effects through the inhibition of the MAPK/JNK signaling pathway mediated by the S1 protein","authors":"Shuiping Liu, Yuting Zeng, Dengju Guo, Jinwei Huang, Xi Li, Guihong Zhang","doi":"10.1016/j.vetmic.2025.110858","DOIUrl":"10.1016/j.vetmic.2025.110858","url":null,"abstract":"<div><div>Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a porcine intestinal alpha coronavirus that infects newborn piglets. Clinical symptoms include acute diarrhea, vomiting, dehydration, and death. There is no effective prevention and control vaccine yet, so new measures are urgently needed, including antiviral strategies. Astragaloside IV (AS-IV) has several pharmacological properties, including immunomodulatory, anti-inflammatory, and antiviral effects. This research found that AS-IV inhibited SADS-CoV replication in vitro through antagonizing the MAPK/JNK pathway mediated by SADS-CoV S1 protein and reducing apoptosis. In addition, SADS-CoV S1 protein interacted with RPSA to activate MAPK/JNK pathway to facilitate virus replication. AS-IV reduced the clinical symptoms and intestinal pathological damage caused by SADS-CoV infection. AS-IV significantly reduced the viral loads in the intestinal tissue and anal swabs, and increased survival of infected piglets, suggesting that AS-IV is a potential antiviral drug for the prevention and control of SADS-CoV. Additionally, in vitro and in vivo experiments showed that AS-IV downregulated the levels of inflammatory factors, including IL-1β, IL-6, IL-8 and TNF-α, indicating that AS-IV ameliorated SADS-CoV infection-induced inflammatory response. In conclusion AS-IV exerts antiviral effects and anti-inflammatory responses through inhibiting the MAPK/JNK signaling pathway mediated by SADS-CoV S1. This study provides a theoretical basis for the research and development of anti-SADS-CoV drugs.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"313 ","pages":"Article 110858"},"PeriodicalIF":2.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885545","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

Copper-based drugs inhibit infectious bronchitis virus (IBV) in vitro and in vivo 铜基药物体外和体内抑制传染性支气管炎病毒（IBV）

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2025-12-29 DOI: 10.1016/j.vetmic.2025.110857

Lisen Lin , Jiaqi Li , Chao Shang , Dapeng Li , Mingzhe Sun , Gaojie Song , Guangbo Qu , Xiao Li , Ran Zhu , Cuiling Zhang , Qinghao He , Guibin Jiang

Infectious bronchitis (IB) is an acute respiratory disease caused by the infectious bronchitis virus (IBV), spreads rapidly and manifests with diverse clinical signs, posing a major significant to the poultry industry. Metal ions such as copper are known to possess notable antiviral properties. Therefore, we evaluated the potential efficacy of copper-based pharmaceuticals against IBV. Results demonstrated that the copper-based drugs significantly protected DF-1 cells from IBV-M41 infection, markedly increasing cell activity and reducing IBV N-gene level. Furthermore, these drugs enhanced antiviral immunity and exhibited anti-apoptotic activity in vitro. In addition, these drugs increased the survival rates of infected chicken embryos and chicks while reducing developmental disruptions, thereby demonstrating robust antiviral effects. Pathological examinations revealed that lesions in the lungs, trachea, kidneys, spleen and other organs of treated groups improved to varying degrees, with a down-regulation of IBV N-gene level in chicks. Our study showed that the copper-based drugs exhibited anti-IBV-M41 both in vitro and in vivo, which provides a theoretical and experimental basis for exploring the anti-coronaviral effects of metal-based drug candidates.

传染性支气管炎（IB）是由传染性支气管炎病毒（IBV）引起的一种急性呼吸道疾病，传播迅速，临床症状多样，对家禽业造成重大影响。众所周知，铜等金属离子具有显著的抗病毒特性。因此，我们评估了铜基药物对IBV的潜在疗效。结果表明，铜基药物能显著保护DF-1细胞免受IBV- m41感染，显著提高细胞活性，降低IBV n基因水平。此外，这些药物在体外增强抗病毒免疫并表现出抗凋亡活性。此外，这些药物增加了受感染鸡胚胎和雏鸡的存活率，同时减少了发育中断，从而显示出强大的抗病毒作用。病理检查显示，处理组雏鸡肺、气管、肾、脾等脏器病变均有不同程度改善，IBV n基因水平下调。我们的研究表明，铜基药物在体外和体内均表现出抗ibv - m41的活性，这为探索金属基候选药物的抗冠状病毒作用提供了理论和实验基础。

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引用次数: 0