Veterinary microbiology最新文献_第3页

African swine fever virus pNP419L inhibits host translation and increases viral replication through the PERK/eIF2α pathway 非洲猪瘟病毒pNP419L通过PERK/eIF2α途径抑制宿主翻译并增加病毒复制。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-31 DOI: 10.1016/j.vetmic.2026.110920

Xueying Wang , Zixuan Wang , Yilin Guo , Sai Niu , Rui Liang , Lin Cheng , Hakimeh Baghaei Daemi , Guiqing Peng

African swine fever (ASF) is a highly contagious disease caused by African swine fever virus (ASFV), which poses a significant threat to pig farming worldwide. Although ASFV encodes many self-sustaining proteins, its mRNA translation relies on the host’s translation machinery. However, the mechanisms by which ASFV-encoded proteins regulate the host’s translation process in infected cells remain largely unexplored. In this study, we investigated how ASFV-encoded proteins affect the translation of host cells. We identified 21 ASFV genes, excluding those from multigene families, that significantly inhibited Renilla luciferase (Rluc) activity. Among these genes, only NP419L, which is known as an early-expressed gene, demonstrated a strong inhibitory effect. We showed that NP419L significantly suppressed host protein synthesis, independent of its enzymatic activity. Our study, which utilized confocal microscopy and biochemical assays, revealed significant implications for ASFV infection. We found that ASFV pNP419L localized to the endoplasmic reticulum (ER), induced ER stress and activated the PERK/eIF2α pathway, resulting in the inhibition of host translation. Furthermore, viral assays demonstrated that knockdown of NP419L effectively reduced viral replication and significantly restored host gene expression. Overall, our findings improve the understanding of how the ASFV protein inhibits host translation and reveal a novel function of ASFV pNP419L beyond its DNA ligase activity for the first time, providing critical insights into translational regulation during ASFV infection.

非洲猪瘟（ASF）是由非洲猪瘟病毒（ASFV）引起的一种高度传染性疾病，对世界范围内的养猪业构成重大威胁。尽管ASFV编码许多自我维持的蛋白质，但其mRNA的翻译依赖于宿主的翻译机制。然而，asfv编码蛋白在感染细胞中调控宿主翻译过程的机制在很大程度上仍未被探索。在这项研究中，我们研究了asfv编码蛋白如何影响宿主细胞的翻译。我们鉴定出21个ASFV基因（不包括来自多基因家族的基因）显著抑制Renilla荧光素酶（Rluc）活性。在这些基因中，只有被称为早期表达基因的NP419L表现出较强的抑制作用。我们发现NP419L显著抑制宿主蛋白合成，独立于其酶活性。我们的研究利用共聚焦显微镜和生化分析，揭示了ASFV感染的重要意义。我们发现ASFV pNP419L定位于内质网（ER），诱导内质网应激并激活PERK/eIF2α通路，从而抑制宿主翻译。此外，病毒实验表明，敲除NP419L可有效减少病毒复制并显著恢复宿主基因表达。总的来说，我们的研究结果提高了对ASFV蛋白如何抑制宿主翻译的理解，并首次揭示了ASFV pNP419L在其DNA连接酶活性之外的新功能，为ASFV感染期间的翻译调控提供了重要见解。

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引用次数: 0

Activating FcγRI inhibits RIG-I-mediated host antiviral innate immunity by FGR during PRRSV-ADE infection 激活fc γ - ri可抑制PRRSV-ADE感染期间FGR介导的rig - i介导的宿主抗病毒先天免疫

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110913

Peng-li Xu , Yi-han Li , Fa-hao Li , Shi-jie Zhao , Wen Li , Jing Chen , Ping-an Xia , Yi-na Zhang

Currently, the antibody-dependent enhancement (ADE) effect has been a pivotal factor in the persistent infection of pigs with porcine reproductive and respiratory syndrome virus (PRRSV) and a major hurdle in developing safe and effective vaccines. Therefore, elucidating the molecular mechanisms of ADE in PRRSV infection is crucial. This study assessed the impact of Fc gamma receptor I (FcγRI), Fc epsilon receptor gamma chain (FCER1G), and FGR on the host's antiviral innate immune response during PRRSV-ADE infection in vitro. Our results revealed that the expressions of RIG-I, TBK-1, IRF-3, STAT-1, and STAT-2 were markedly inhibited in porcine alveolar macrophages (PAMs) via ADE. Furthermore, the production of IFN-α, ISG15, ISG56, OAS1, OAS2, Mx1, and RSAD2 were dramatically decreased during PRRSV-ADE infection. Additionally, gene knockdown studies indicated that PRRSV-ADE infection upregulates FGR expression by activating FcγRI. Moreover, knocking down endogenous FcγRI, FCER1G, or FGR alleviated the inhibitory effect of PRRSV-ADE infection on the RIG-I-mediated antiviral innate immune response in PAMs. Thus, our findings demonstrate that activation FcγRI could suppress RIG-I-mediated antiviral innate immune response through FGR during PRRSV-ADE infection, thereby facilitating viral replication. These insights enhance our understanding of the molecular mechanism of underlying intrinsic ADE (iADE) and could contribute to the design of novel PRRSV vaccine.

目前，抗体依赖性增强（ADE）效应是猪繁殖与呼吸综合征病毒（PRRSV）持续感染的关键因素，也是开发安全有效疫苗的主要障碍。因此，阐明ADE在PRRSV感染中的分子机制至关重要。本研究在体外研究了Fcγ受体I （Fcγ ri）、Fc epsilon受体γ链（FCER1G）和FGR对PRRSV-ADE感染时宿主抗病毒先天免疫反应的影响。结果表明，ADE可显著抑制猪肺泡巨噬细胞（PAMs）中rig -1、TBK-1、IRF-3、STAT-1和STAT-2的表达。此外，在PRRSV-ADE感染期间，IFN-α、ISG15、ISG56、OAS1、OAS2、Mx1和RSAD2的产生显著降低。此外，基因敲低研究表明，PRRSV-ADE感染通过激活fc - γ - ri上调FGR表达。此外，敲低内源性fc - γ - ri、FCER1G或FGR可减轻PRRSV-ADE感染对PAMs中rig - i介导的抗病毒先天免疫反应的抑制作用。因此，我们的研究结果表明，激活fc γ - ri可以在PRRSV-ADE感染期间通过FGR抑制rig - i介导的抗病毒先天免疫反应，从而促进病毒复制。这些见解增强了我们对潜在的内在ADE （iADE）的分子机制的理解，并可能有助于设计新的PRRSV疫苗。

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引用次数: 0

Rotavirus induces mucosal B-cell responses through the TLR3/TRIF and MAVS pathways 轮状病毒通过TLR3/TRIF和MAVS途径诱导粘膜b细胞应答。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110910

Rong-Rong Zhang, Yong-Yi Yang, Man Wang, Wen-Ru Yang, Riaz Muhammad Azeem, Fu-Xuan Niu, Ya-Xin Yang, Man-Jie Hu, Chun-Wei Shi, Gui-Lian Yang, Hai-Bin Huang, Jian-Zhong Wang, Yan-Long Jiang, Xin Cao, Nan Wang, Yan Zeng, Wen-Tao Yang, Chun-Feng Wang

Rotavirus (RV) infection is a zoonotic disease that causes severe diarrhea in young mammals and humans and is spreading globally. The TLR3/TRIF and RIG-I/MAVS signaling pathways are activated upon recognition of double-stranded RNA (dsRNA) and play crucial roles in the host antiviral response during RV infection. However, the mechanism by which RV induces B-cell immune responses through TLR3 and RIG-I signaling remains unclear. Here, T-cell receptor (TCR) sequencing results revealed that TRIF gene deletion affects the frequency of complementarity-determining region 3 (CDR3) clones recognizing antigen peptides presented by MHC-II on B cells and the utilization of V and J genes in mouse CD4⁺ T cells. Specifically, a reduced frequency of germinal center (GC)-activated B cells was observed in the mesenteric lymph nodes (MLNs) of TLR3^-/-, TRIF^-/-, and MAVS^-/- mice. Similarly, the levels of antibodies secreted by B cells in serum and CD138⁺IgA⁺ cells in the small intestine decreased. The simultaneous absence of the TLR3 and MAVS genes weakened the proliferative capacity of B cells. This study elucidates the mechanism by which RV regulates B-cell immunity through the TLR3/TRIF and MAVS signaling pathways, providing theoretical basis for novel vaccine development.

轮状病毒（RV）感染是一种在幼龄哺乳动物和人类中引起严重腹泻的人畜共患疾病，并正在全球传播。TLR3/TRIF和RIG-I/MAVS信号通路在识别双链RNA （dsRNA）时被激活，并在RV感染期间宿主抗病毒反应中发挥关键作用。然而，RV通过TLR3和rig - 1信号诱导b细胞免疫应答的机制尚不清楚。这里，T细胞受体（TCR）测序结果显示，TRIF基因缺失会影响B细胞上识别MHC-II呈递抗原肽的互补决定区3 （CDR3）克隆的频率，以及小鼠CD4+ T细胞中V和J基因的利用。具体来说，在TLR3-/-、TRIF-/-和MAVS-/-小鼠的肠系膜淋巴结（MLNs）中观察到生发中心（GC）激活的B细胞频率降低。同样，血清中B细胞和小肠中CD138+IgA+细胞分泌的抗体水平下降。TLR3和MAVS基因同时缺失会削弱B细胞的增殖能力。本研究阐明了RV通过TLR3/TRIF和MAVS信号通路调控b细胞免疫的机制，为新型疫苗的研制提供理论依据。

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引用次数: 0

Haemaphysalis longicornis ticks as a competent vector for ‘Candidatus Mycoplasma haemobos’ in experimental transmission studies 长角血蜱作为“候选血支原体”的有效媒介在实验传播研究中的应用。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110915

Hongfei Shi, Jingjing Mao, Hongyue Zhai, Zhengtian Zhang, Li Wang, Dandan Li, Lunguang Yao

‘Candidatus Mycoplasma haemobos’ (‘Ca. M. haemobos’) is an emerging hemotrophic mycoplasma affecting cattle and other animals worldwide. While arthropod vectors have been suspected in its transmission, experimental evidence confirming vector competence remains limited. We investigated the ability of the hard tick Haemaphysalis longicornis (H. longicornis) to acquire, maintain, and transmit ‘Ca. M. haemobos’ under laboratory conditions. Ticks were exposed to the pathogen via microinjection or by feeding on infected BALB/c mice. Transovarial and transstadial transmission were assessed using quantitative PCR detection across tick life stages. All developmental stages (larvae, nymphs, adults) acquired the pathogen after feeding on infected mice, with infection rates in larvae and nymphs increasing significantly over 14 days. Microinjected adults maintained high pathogen loads for up to 28 days. Transovarial transmission was demonstrated, with 68.4 % of egg pools and 84.9 % of larval pools testing positive. Transstadial transmission was also observed, with pathogen persistence and significant replication during the larval-to-nymph molt. In transmission trials, larvae, nymphs, and adults successfully infected mice, with efficiencies of 80.0 %, 70.0 %, and 80.0 %, respectively. Adult ticks induced significantly higher bacteremia in hosts compared to larvae. This study provides the first experimental evidence that H. longicornis is a competent vector for ‘Ca. M. haemobos’, capable of both transovarial and transstadial transmission, and maintaining the pathogen throughout its life cycle. These findings underscore the role of H. longicornis in the ecology and transmission of ‘Ca. M. haemobos’, with significant implications for disease control in endemic regions.

“候选血支原体”（“Ca. M. haemobos”）是一种影响全世界牛和其他动物的新出现的血液营养支原体。虽然节肢动物媒介被怀疑是其传播媒介，但证实媒介能力的实验证据仍然有限。我们调查了长角血蜱（长角血蜱）在实验室条件下获取、维持和传播“血杆菌”的能力。蜱虫通过微量注射或以感染的BALB/c小鼠为食暴露于病原体。通过蜱虫生命阶段的定量PCR检测评估经卵巢和经卵巢传播。所有发育阶段（幼虫、若虫、成虫）均在摄食感染的小鼠后获得病原体，在14 d内，幼虫和若虫的感染率显著增加。微注射成虫保持高病原体负荷长达28天。经卵巢传播，卵池阳性率为68.4% %，幼虫池阳性率为84.9% %。在幼虫到若虫的蜕皮过程中，也观察到病原体的持续传播和显著的复制。在传播试验中，幼虫、若虫和成虫成功感染小鼠，感染效率分别为80.0 %、70.0 %和80.0 %。与幼虫相比，成年蜱在宿主中引起明显更高的菌血症。该研究首次提供了实验证据，证明长角锥虫是“嗜血杆菌”的有效载体，能够跨卵巢和跨体位传播，并在其整个生命周期中维持病原体。这些发现强调了长角锥虫在“嗜血杆菌”的生态学和传播中的作用，对流行地区的疾病控制具有重要意义。

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引用次数: 0

Engineering of recombinant porcine deltacoronavirus stably expressing foreign gene. 稳定表达外源基因的重组猪冠状病毒工程研究。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110918

Meng Yuan, Yuhan Zhang, Longfei Chen, Shaobo Xiao, Liurong Fang

Porcine deltacoronavirus (PDCoV) is an emerging enteric virus characterized by high viral titers, strong immunogenicity, and broad host tropism, making it a promising candidate for developing vaccine vectors and foreign gene expression platforms. However, key aspects such as its transcription regulatory sequence (TRS) usage, reliable insertion sites, and the genetic stability of recombinant viruses remain incompletely understood. In this study, we established a reverse genetic system for the PDCoV strain DHeB1 and systematically evaluated the transcriptional activity of six TRS elements from the S, E, M, N, NS6, and NS7 genes. Each TRS was used to drive the expression of EGFP inserted between the N gene and 3' UTR of viral genome. The results showed that all TRSs could initiate EGFP expression, with the NS6-derived TRS exhibiting the strongest activity. However, all recombinant viruses carrying the EGFP cassette exhibited genetic instability, being passaged only up to seven times in LLC-PK1 cells, indicating that the region between the N gene and 3' UTR is unsuitable for stable foreign gene insertion. To improve genetic stability, while leveraging the strong promoter activity identified, we replaced the NS6 gene with the EGFP gene, as NS6 is an accessory protein whose deletion does not terminate viral replication. This recombinant virus was successfully rescued and stably propagated in LLC-PK1 cells for at least 15 passages, maintaining consistent EGFP expression. Collectively, this study provides an efficient reverse genetics platform for PDCoV, characterizes the transcriptional regulation of its TRS elements, and demonstrates the generation of a stable recombinant PDCoV expressing a foreign gene, thereby facilitating the development of PDCoV-based vector systems.

猪三角冠状病毒（PDCoV）是一种新兴的肠道病毒，具有高滴度、强免疫原性和广泛的宿主亲和性，是开发疫苗载体和外源基因表达平台的有希望的候选病毒。然而，其转录调控序列（TRS）的使用、可靠的插入位点和重组病毒的遗传稳定性等关键方面仍未完全了解。在本研究中，我们建立了PDCoV菌株DHeB1的反向遗传系统，系统地评估了S、E、M、N、NS6和NS7基因中6个TRS元件的转录活性。每个TRS用于驱动插入病毒基因组N基因和3' UTR之间的EGFP的表达。结果表明，所有TRS均能启动EGFP表达，其中ns6衍生的TRS活性最强。然而，所有携带EGFP盒的重组病毒都表现出遗传不稳定性，在LLC-PK1细胞中传代最多7次，这表明N基因和3' UTR之间的区域不适合稳定的外源基因插入。为了提高遗传稳定性，在利用已发现的强启动子活性的同时，我们将NS6基因替换为EGFP基因，因为NS6是一种辅助蛋白，其缺失不会终止病毒复制。该重组病毒成功获救，并在LLC-PK1细胞中稳定繁殖了至少15代，保持了一致的EGFP表达。总之，本研究为PDCoV提供了一个高效的反向遗传平台，表征了其TRS元件的转录调控，并证明了表达外源基因的稳定重组PDCoV的产生，从而促进了基于PDCoV的载体系统的发展。

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引用次数: 0

Seneca Valley virus 2B and 3 C proteins attenuate the cGAS-STING signaling pathway by targeting STING for degradation. 塞内卡谷病毒2B和3 C蛋白通过靶向STING降解来减弱cGAS-STING信号通路。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110911

Xuexia Wen, Meijun Zhou, Shijie Xie, Jin Yuan, Yu Hong, Ruiyi Ma, Liwei Zhao, Dan Wang, Rong Quan, Peipei Cheng, Jiangwei Song

Seneca Valley virus (SVV), an emerging porcine picornavirus, has attracted significant attention recently as it presents a substantial threat to the global pork industry. Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER)-associated adaptor protein that plays a crucial role in the type I interferon (IFN-I) signaling pathway, which triggers IFN-stimulated gene (ISG) production to elicit antiviral innate immunity. SVV has evolved numerous strategies to counteract the IFN-I signaling pathway and evade innate immunity. However, the mechanism underlying immune evasion in SVV infection remains unclear. In this study, we observed that SVV 2B and 3 C protease (3 C^pro) proteins promoted STING degradation to antagonize IFN-I activation through autophagy and caspase pathways, respectively. Mechanistically, 2B bound to STING, recruiting toll-interacting protein (Tollip) and neighbor of BRCA1 gene 1 (NBR1) to promote STING for autophagy degradation, and 2B prevented the STING-TBK1 interaction. Furthermore, SVV 3 C^pro antagonized host IFN-I signaling by cleaving interferon-stimulated gene 60 (ISG60) at Gln-406. The cleaved ISG60 products failed to inhibit SVV infection. Collectively, our study uncovered that SVV subverts the IFN-I response by targeting STING and ISG60, providing deeper insights into a novel mechanism utilized by SVV to antagonize the host's innate immune response.

塞内卡谷病毒（SVV）是一种新兴的猪小核糖核酸病毒，最近引起了极大的关注，因为它对全球猪肉产业构成了重大威胁。干扰素基因刺激因子（STING）是一种内质网（ER）相关的衔接蛋白，在I型干扰素（IFN-I）信号通路中起着至关重要的作用，它触发ifn刺激基因（ISG）的产生，从而引发抗病毒先天免疫。SVV已经进化出许多策略来对抗IFN-I信号通路并逃避先天免疫。然而，SVV感染的免疫逃避机制尚不清楚。在本研究中，我们观察到SVV 2B和3 C蛋白酶（3 Cpro）蛋白分别通过自噬和caspase途径促进STING降解以拮抗IFN-I活化。从机制上讲，2B与STING结合，招募toll-相互作用蛋白（Tollip）和BRCA1基因1的邻居（NBR1），促进STING自噬降解，2B阻止STING- tbk1相互作用。此外，SVV 3 Cpro通过在Gln-406位点切割干扰素刺激基因60 （ISG60）来拮抗宿主IFN-I信号。裂解后的ISG60产物未能抑制SVV感染。总的来说，我们的研究发现SVV通过靶向STING和ISG60来破坏IFN-I反应，这为SVV拮抗宿主先天免疫反应的新机制提供了更深入的见解。

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引用次数: 0

Replacement of the Loop 4 region in CPV VP2 with corresponding PPV segments affects N-terminal cleavage, VLP morphology, hemagglutination, and cell binding 用相应的PPV片段替换CPV VP2中的Loop 4区域会影响n端切割、VLP形态、血凝和细胞结合。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110919

Shengke Chang , Wenjun Meng , Jie Li , Cun Qu , Na Li , Rongjun Wang

Canine parvovirus (CPV) and porcine parvovirus (PPV) are closely related Protoparvoviruses whose major capsid protein VP2 is essential for virus-like particle (VLP) assembly and hemagglutination (HA). To investigate structural determinants of VP2 function, two chimeric CPV VP2 constructs were generated by replacing the Loop 4 region with the corresponding PPV segment, either in full-length (CL) or truncated (CTL) form. SDS-PAGE and western blotting revealed complete N-terminal cleavage of VP2 into VP3 in both constructs. Electron microscopy showed that CL VLPs had increased diameters, whereas CTL VLPs formed defective particles with reduced size and irregular morphology. HA activity was abolished in both chimeric VLPs. Cell binding assays with CL VLPs demonstrated that Loop 4 substitution caused loss of attachment to F81 cells (feline kidney cell line) and PK15 cells (porcine kidney cell line), whereas wild-type CPV VP2 and PPV VP2 VLPs retained their respective cell-specific binding. These results demonstrated that Loop 4 was a critical determinant for maintaining capsid structural integrity and functional orientation, including particle size regulation, HA, and VLP-cell interactions. This study provided mechanistic insights into how conformational perturbations or structural defects in the three-fold spike affected viral function, offering a framework for dissecting VP2 structural and functional divergence across Protoparvoviruses.

犬细小病毒（CPV）和猪细小病毒（PPV）是亲缘关系密切的原细小病毒，其主要衣壳蛋白VP2是病毒样颗粒（VLP）组装和血凝（HA）所必需的。为了研究VP2功能的结构决定因素，用全长（CL）或截短（CTL）形式的PPV片段替换Loop 4区域，生成了两个嵌合CPV VP2构建体。SDS-PAGE和western blotting显示两种结构的VP2的n端完全裂解为VP3。电镜显示，CL VLPs直径增大，而CTL VLPs形成缺陷颗粒，尺寸减小，形态不规则。在两种嵌合VLPs中，HA活性均被消除。与CL VLPs的细胞结合实验表明，环4替代导致F81细胞（猫肾细胞系）和PK15细胞（猪肾细胞系）的附着丧失，而野生型CPV VP2和PPV VP2 VLPs保留了各自的细胞特异性结合。这些结果表明，环路4是维持衣壳结构完整性和功能取向的关键决定因素，包括粒径调节、HA和vlp -细胞相互作用。该研究提供了三倍尖刺的构象扰动或结构缺陷如何影响病毒功能的机制见解，为解剖原细小病毒VP2结构和功能差异提供了框架。

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引用次数: 0

The role of neuraminidase NanH in drug-induced phagocytic resistance of G. parasuis and its targeted intervention 神经氨酸酶NanH在副猪螺旋体药物性吞噬耐药中的作用及其靶向干预。

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110905

Yuqing Tan , Ze Li , Shijiao Huan , Yaqin Liu , Hengming Liu , Shenglan Liu , Zhixin Lei

Background

Glaesserella parasuis (G. parasuis) is the core pathogen of porcine respiratory disease syndrome (PRDC), and the co-evolution of its drug resistance and virulence has seriously threatened the biosecurity of the global pig farming industry.

Objective

This study aims to clarify the core function of neuraminidase (NanH) in the formation and pathogenic mechanism of G. parasuis resistance and explore its feasibility as a novel therapeutic target.

Method

Drug-resistant strains were induced by tildipirosin combined with florfenicol (MIC increased to 16 μg/mL), and the mechanism of drug resistance was systematically analyzed by transcriptomics, gene knockout and multi-model infection experiments.

Result

The activity of the ABC transport system in drug-resistant strains was enhanced, the virulence genes VapC and artM were upregulated, the smoothness of the cell wall increased, and host autophagy was significantly inhibited (LC3-II transformation decreased, P < 0.01). The nanH gene was highly expressed in drug-resistant strains. Its deletion (ΔnanH) reduced bacterial adhesion by 57 % (P < 0.01), decreased mouse mortality by 70 % (P < 0.005), and inhibited the transcription of COX-2 and TNF-α. The autophagy-targeted chimeric (NanH-AUTAC) designed based on the targeted protein degradation (TPD) strategy achieved a degradation rate of 60 % for NanH-EGFP at 40 μM.

Conclusion

NanH is a key regulatory factor in the co-evolution of G. parasuis drug resistance and virulence, and can serve as a potential target for anti-infection treatment. The "disarming" strategy based on TPD provides a new direction for dealing with drug-resistant bacterial infections.

背景：副猪Glaesserella parasuis （G. parasuis）是猪呼吸系统疾病综合征（PRDC）的核心病原体，其耐药性和毒力的共同进化严重威胁着全球养猪业的生物安全。目的：阐明神经氨酸酶（NanH）在副猪螺旋体耐药形成中的核心作用及其致病机制，探讨其作为新型治疗靶点的可行性。方法：采用替地匹罗辛联合氟苯尼考诱导耐药菌株（MIC升高至16 μg/mL），通过转录组学、基因敲除和多模型感染实验系统分析耐药机制。结果：耐药菌株ABC转运系统活性增强，毒力基因VapC和artM表达上调，细胞壁平滑度增加，宿主自噬明显受到抑制(LC3-II转化减少，P 结论：NanH是副猪螺旋体耐药和毒力协同进化的关键调控因子，可作为抗感染治疗的潜在靶点。基于TPD的“解除武装”策略为处理耐药细菌感染提供了新的方向。

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引用次数: 0

Distinct mechanisms of ER stress-mediated autophagy induction by high- and low-virulence pseudorabies virus strains 高毒力和低毒力伪狂犬病毒株内质网应激诱导自噬的不同机制

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110914

Yueqing Lv , Xiangmei Huang , Zhipei Lu , Xiaoying Feng , Kang Ouyang , Ying Chen , Zuzhang Wei , Weijian Huang , Yifeng Qin

Pseudorabies virus (PRV) is one of the most significant pathogens threatening the swine industry, and its infection has caused substantial economic losses to pig farming worldwide. This study utilized two PRV strains isolated by our laboratory: the GXLB-2015 strain, a natural recombinant between a PRV variant strain and the Bartha-K61 vaccine strain, which exhibits stronger virulence, and the GXGG-2016 strain, a classical genotype II PRV strain with a natural 69-amino acid deletion in its TK gene, which demonstrates weak virulence and is non-pathogenic in mice. Focusing on endoplasmic reticulum stress (ERS) and cellular autophagy, this research explored the molecular mechanisms underlying the significant difference in virulence between these two PRV strains. The results revealed that infection with both strains induced noticeable ERS and autophagy, both of which inhibited viral replication. Further investigation showed that upon ERS induction, the GXLB-2015 strain mediated autophagy by activating both the PERK-eIF2α-ATF4-CHOP and IRE1-XBP1 pathways; inhibiting these pathways suppressed viral replication. In contrast, the GXGG-2016 strain infection mediated autophagy primarily through activating only the IRE1-XBP1 pathway, and inhibiting this pathway had no significant impact on viral replication. These findings indicate that while PRV infection can induce cellular autophagy by activating ERS, the specific unfolded protein response (UPR) pathways involved differ significantly between strains of varying virulence. This study provides a foundation for understanding the pathogenesis of different PRV strains and developing novel antiviral drugs.

伪狂犬病毒（PRV）是威胁养猪业最重要的病原体之一，其感染给世界范围内的养猪业造成了巨大的经济损失。本研究采用本实验室分离的两株PRV: GXLB-2015株是PRV变异株与Bartha-K61疫苗株之间的天然重组株，具有较强的毒力；GXGG-2016株是典型的基因II型PRV株，其TK基因天然缺失69个氨基酸，毒力弱，对小鼠无致病性。本研究以内质网应激（endoplasmic reticulum stress， ERS）和细胞自噬为研究重点，探讨了两种PRV毒株毒力显著差异的分子机制。结果表明，这两种菌株的感染均诱导了明显的ERS和自噬，两者均抑制了病毒复制。进一步研究发现，在ERS诱导下，GXLB-2015菌株通过激活PERK-eIF2α-ATF4-CHOP和IRE1-XBP1通路介导自噬；抑制这些途径可抑制病毒复制。相比之下，GXGG-2016菌株感染主要通过激活IRE1-XBP1途径介导自噬，抑制该途径对病毒复制无显著影响。这些发现表明，虽然PRV感染可以通过激活ERS诱导细胞自噬，但所涉及的特异性未折叠蛋白反应（UPR）途径在不同毒力的菌株之间存在显著差异。该研究为了解不同PRV毒株的发病机制和开发新型抗病毒药物提供了基础。

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引用次数: 0

Prevalence and diversity of non-tuberculous mycobacteria isolated from slaughtered tuberculin-positive bovine samples: Epidemiological and Diagnostic implications 从屠宰结核菌阳性牛样本中分离出的非结核分枝杆菌的患病率和多样性：流行病学和诊断意义

IF 2.7 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology

Pub Date : 2026-01-29 DOI: 10.1016/j.vetmic.2026.110909

Natalia Jiménez-Pizarro , David Risco , Felipe Molina , Remigio Martínez , Alfredo García , José Manuel Benítez-Medina , Javier Hermoso-de-Mendoza

The isolation of non-tuberculous mycobacteria (NTM) is common in cattle positive for tuberculosis (TB) in official diagnostic tests, whereas data on specific NTM species in Spanish cattle remain limited. This study identifies the most frequently isolated NTM species from Single Intradermal Tuberculin Test (SITT)-positive cattle in Extremadura, western Spain. Among 1669 Mycobacterium Growth Indicator Tube (MGIT) positive cultures collected in 2018, 493 (29.54 %) were identified as NTM, and 194 were randomly selected for further analysis. Polymerase Chain Reaction (PCR)-restriction analysis of the hsp65 gene and partial sequencing of 16S ribosomal DNA (rDNA) confirmed a diverse range of species. The most prevalent complex was Mycobacterium avium (40.12 %), including M. senriense, M. intracellulare, and M. avium subsp. paratuberculosis. Other notable NTM species (23.35 %) included M. bourgelatii, M. kansasii, M. gordonae, and M. shinjukuense. Less frequent complexes included M. simiae (11.38 %), M. ulcerans (3.59 %), M. parafortuitum (2.99 %), and M. terrae (1.20 %), along with M. holsaticum (1.20 %), a species related to the M. tuberculosis complex. Phylogenetic analysis and geographic mapping revealed weak correlation between genetic and geographic distances (Mantel test: R_xy = 0.015, P = 0.253), suggesting limited spatial structuration of genetic diversity. Alpha diversity metrics indicated moderate diversity (Shannon’s H = 2.641, Simpson’s D = 0.106), with some zones exhibiting greater species evenness. Diversity analyses showed moderate dissimilarity among clusters. These findings enhance understanding of Mycobacterium diversity and distribution while emphasizing the diagnostic challenges posed by NTM in TB detection and the importance of molecular tools in species identification and epidemiological surveillance.

非结核分枝杆菌（NTM）的分离在官方诊断测试中结核病（TB）阳性的牛中很常见，而西班牙牛中特定NTM物种的数据仍然有限。本研究确定了西班牙西部埃斯特雷马杜拉单一皮内结核菌素试验（SITT）阳性牛中最常分离的NTM物种。在2018年收集的1669株分枝杆菌生长指示管（MGIT）阳性培养物中，鉴定为NTM的有493株（29.54 %），随机抽取194株进行进一步分析。聚合酶链反应(PCR)- hsp65基因的限制性分析和16S核糖体DNA （rDNA）的部分测序证实了物种的多样性。最常见的复体是鸟分枝杆菌（40.12 %），包括senriense分枝杆菌、胞内分枝杆菌和鸟分枝杆菌亚种。副结核。其他显著的NTM种包括布氏支原体、甘肃支原体、戈登支原体和新injukuense支原体（23.35 %）。较不常见的复合体包括相似分枝杆菌（11.38 %）、溃疡分枝杆菌（3.59 %）、副fortuitum分枝杆菌（2.99 %）和地分枝杆菌（1.20 %），以及与结核分枝杆菌复合体相关的holsatium分枝杆菌（1.20 %）。系统发育分析和地理图谱显示，遗传多样性与地理距离的相关性较弱（Mantel检验：Rxy = 0.015, P = 0.253），表明遗传多样性的空间结构有限。α多样性指标表现为中等水平（Shannon’s H = 2.641, Simpson’s D = 0.106），部分地区物种均匀度较高。多样性分析显示集群间存在适度差异。这些发现加强了对分枝杆菌多样性和分布的认识，同时强调了结核分枝杆菌在结核病检测中的诊断挑战以及分子工具在物种鉴定和流行病学监测中的重要性。

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引用次数: 0