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Genome isomerization of Turkey herpesvirus: Identification of inverted unique short genomes and demonstration of protective efficacy against Marek’s Disease using BAC clones 火鸡疱疹病毒的基因组异构化:倒置独特短基因组的鉴定和使用BAC克隆对马立克氏病的保护作用
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-21 DOI: 10.1016/j.vetmic.2025.110848
Taejoong Kim, Cari J. Hearn, Stephen J. Spatz
Mardivirus meleagridalpha1 (MeAHV1), commonly known as herpesvirus of turkeys (HVT), was developed as a vaccine against Marek's disease (MD). Beyond its role as an MD vaccine, HVT has been successfully used as a recombinant vaccine vector to protect poultry from various viral, bacterial, and parasitic diseases. To study the process of viral genome concatemerization during HVT replication, the full-length genome of the HVT Fc126 strain was cloned into a bacterial artificial chromosome (BAC) by inserting a mini-F cassette. Full-length sequencing of three recombinant HVT-BAC clones was performed using long-read next-generation sequencing. The resulting genomic sequences were compared to the published HVT reference genome. HVT-BAC#1 and HVT-BAC#2 showed 95.8 % and 95.6 % identity, respectively, while HVT-BAC#3 had a 99.4 % identity. Further analysis revealed that HVT-BAC#1 and HVT-BAC#2 contained an inverted unique short (US) subgenomic region, classifying them as the Inverted short (IS) isomer, whereas HVT-BAC#3 had a prototype (P) genome arrangement. In silico inversion of the US region in HVT-BACs #1 and HVT-BAC#2 increased their sequence identity to the reference to 99.4 % and 99.5 %, respectively. In addition, all three HVT-BACs constructed in this study contained deletions encompassing the HVT071 ORF and the 5′ end of the HVT070 ORF. The IS and P genomes of HVT-BAC were re-isolated from the DNA of HVT-BAC#1 reconstituted viruses infected cells. Regardless of the variable genomic structure of HVT-BAC clones, the protective efficacy of the two HVT-BAC-derived viruses was slightly better than that of the parental HVT in Rep2, but it was not significantly different from that of the parental HVT in Rep1 against virulent Marek’s disease virus challenge. These data have confirmed the variability of the MeAHV1 genome in isomerization during replication.
火鸡病毒性肝炎病毒(MeAHV1),俗称火鸡疱疹病毒(HVT),是一种针对马立克病(MD)的疫苗。除了作为MD疫苗的作用外,HVT还成功地用作重组疫苗载体,以保护家禽免受各种病毒、细菌和寄生虫病的侵害。为了研究HVT复制过程中病毒基因组的拼接过程,将HVT Fc126株的全长基因组通过插入mini-F卡带克隆到细菌人工染色体(BAC)中。对三个重组HVT-BAC克隆进行长读测序。将得到的基因组序列与已发表的HVT参考基因组进行比较。HVT-BAC#1和HVT-BAC#2的同源性分别为95.8% %和95.6% %,而HVT-BAC#3的同源性为99.4% %。进一步分析表明,HVT-BAC#1和HVT-BAC#2含有一个倒置的独特短(US)亚基因组区域,将它们归类为倒置短(IS)异构体,而HVT-BAC#3具有一个原型(P)基因组排列。hvt - bacs# 1和hvt - bacs# 2中US区域的计算机反演将其序列与参考序列的一致性分别提高到99.4 %和99.5 %。此外,本研究中构建的所有三个hvt - bac都包含包含HVT071 ORF和HVT070 ORF 5'端的缺失。从HVT-BAC#1重组病毒感染细胞的DNA中重新分离HVT-BAC的IS和P基因组。无论HVT- bac克隆的基因组结构如何变化,这两种HVT- bac衍生病毒对马立克病毒攻击的保护作用略优于亲本的Rep2中的HVT,但与亲本的Rep1中的HVT没有显著差异。这些数据证实了MeAHV1基因组在复制过程中异构化的可变性。
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引用次数: 0
PEDV nonstructural protein 14 inhibits RIPK3 and RIPK1-mediated PANoptosis PEDV非结构蛋白14抑制RIPK3和ripk1介导的PANoptosis。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-21 DOI: 10.1016/j.vetmic.2025.110849
Xingyi Xie , Dengkun Wang , Xueke Sun , Xuechen Li , Mengru Luo , Jiahao Cong , Wenju Yuan , Huihui Huang , Zhaojiang Chen , Yuhang Zhang , Zhengjie Kong , Bo Wan
Porcine epidemic diarrhea virus (PEDV) is one of the primary pathogens responsible for severe diarrhea in piglets, causing significant economic losses to the global swine industry. PANoptosis is a critical strategy for the host to resist viral invasion, but the mechanism by which PEDV evades the PANoptosis response remains unclear. In this study, we found that PANoptosis agonists significantly reduce PEDV replication and that PEDV Nsp14 specifically inhibits the activation of the ZBP1-RIPK3-MLKL axis. Mechanistically, we observed that Nsp14 inhibits the promoter activity of RIPK3 and RIPK1, thereby suppressing signal transduction. Additionally, RIPK1 can also recruit Caspase 8 to degrade Nsp14, thereby blocking PEDV replication. Our study reveals the function and mechanism of Nsp14 in PEDV-induced PANoptosis, providing new insights into how PEDV infection and immune evasion.
猪流行性腹泻病毒(PEDV)是导致仔猪严重腹泻的主要病原体之一,给全球养猪业造成重大经济损失。PANoptosis是宿主抵抗病毒入侵的关键策略,但PEDV逃避PANoptosis反应的机制尚不清楚。在本研究中,我们发现PANoptosis激动剂显著降低PEDV复制,PEDV Nsp14特异性抑制ZBP1-RIPK3-MLKL轴的激活。在机制上,我们观察到Nsp14抑制RIPK3和RIPK1的启动子活性,从而抑制信号转导。此外,RIPK1还可以招募Caspase 8来降解Nsp14,从而阻断PEDV的复制。我们的研究揭示了Nsp14在PEDV诱导的PANoptosis中的功能和机制,为PEDV感染和免疫逃避提供了新的见解。
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引用次数: 0
Interactions between Mycoplasma hyopneumoniae strains and the resident lung microbiota in swine 猪肺炎支原体菌株与猪常驻肺微生物群的相互作用
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-16 DOI: 10.1016/j.vetmic.2025.110840
Leonardo Teófilo Toledo , Richard Costa Polveiro , Abelardo Silva-Júnior , Maria Aparecida Scatamburlo Moreira , Fernanda Simone Marks
Enzootic pneumonia (EP) in swine, caused by Mycoplasma hyopneumoniae (M. hyopneumoniae), is a chronic respiratory disease that leads to significant economic losses in pig production. Infection with M. hyopneumoniae can induce pulmonary dysbiosis; however, the impact of different strains with varying degrees of virulence on the composition of a healthy microbiota remains incompletely understood. This study investigated alterations in the lung microbiome of pigs experimentally infected with two distinct strains of M. hyopneumoniae (UFV1 and UFV2) using 16S rRNA gene-based metataxonomic analyses and bioinformatics approaches. Pigs were divided into three experimental groups: Control (uninfected), UFV1 (infected with strain UFV1), and UFV2 (infected with strain UFV2). Bronchoalveolar lavage fluid were collected for DNA extraction and sequencing. Alpha diversity was significantly lower in the infected groups compared to the Control. Beta diversity analysis revealed significant differences in microbiota composition among the groups, with a clear separation between the Control group and the infected groups. Mycoplasma was the most abundant genus in both UFV1 and UFV2 groups, whereas the Control group exhibited greater genus-level diversity, including Stenotrophomonas, Comamonas, and Pseudomonas. Linear discriminant analysis (LDA) confirmed the enrichment of Mycoplasma in the infected groups and identified additional differentially abundant genera. Predictive modeling based on microbiota composition demonstrated high accuracy in classifying the groups, with Varibaculum, Pseudomonas, and Actinobacillus emerging as key genera for prediction. The UFV1 and UFV2 strains exhibited distinct lung microbiota profiles, suggesting different infection dynamics and interactions with the resident microbiota. This study provides new insights into the impact of diverse M. hyopneumoniae strains on the porcine lung microbiome, with implications for the development of preventive and control strategies for EP.
猪流行性肺炎(EP)是由猪肺炎支原体(支原体)引起的一种慢性呼吸道疾病,对养猪生产造成重大经济损失。肺炎支原体感染可引起肺生态失调;然而,具有不同毒力程度的不同菌株对健康微生物群组成的影响仍不完全清楚。本研究利用基于16S rRNA基因的元分类分析和生物信息学方法,研究了猪肺炎支原体两种不同菌株(UFV1和UFV2)实验感染后肺微生物组的变化。将猪分为3个实验组:对照组(未感染)、UFV1组(感染UFV1株)和UFV2组(感染UFV2株)。采集支气管肺泡灌洗液进行DNA提取和测序。与对照组相比,感染组的α多样性显著降低。Beta多样性分析显示各组之间的微生物群组成存在显著差异,对照组和感染组之间存在明显的分离。支原体在UFV1和UFV2组中都是最丰富的属,而对照组则表现出更大的属水平多样性,包括窄养单胞菌、单胞菌和假单胞菌。线性判别分析(LDA)证实了支原体在感染组中的富集,并鉴定了其他差异丰富的属。基于微生物群组成的预测模型在分类类群方面显示出很高的准确性,其中Varibaculum, Pseudomonas和放线菌属成为预测的关键属。UFV1和UFV2菌株表现出不同的肺部微生物群特征,表明不同的感染动态和与常驻微生物群的相互作用。本研究为猪肺炎支原体菌株对猪肺微生物群的影响提供了新的见解,对制定EP的预防和控制策略具有重要意义。
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引用次数: 0
Distribution of antibiotic resistance and virulence genes in Trueperella pyogenes isolated from Korean native cattle 韩国本土牛产化脓性真芽孢杆菌的耐药性和毒力基因分布
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-16 DOI: 10.1016/j.vetmic.2025.110844
Min-Jeong Ji , Youngjun Kim , Kyoung-Seong Choi
Trueperella pyogenes is a commensal and opportunistic pathogen found on the skin and mucous membranes of livestock and wildlife. Although the clinical significance of T. pyogenes in livestock is well recognized, information about this pathogen is scarce in the Republic of Korea (ROK). This study aimed to investigate the distribution of virulence and antibiotic resistance genes in T. pyogenes isolates from clinical infections. A total of 52 T. pyogenes isolates were obtained from cattle with respiratory distress or suppurative infections across five different farms in the ROK. PCR assays were used to detect virulence and antibiotic resistance genes, and antimicrobial susceptibility testing was performed using the disk diffusion method. Among the virulence genes, plo was detected in all isolates (100 %), followed by cbpA (65.4 %), fimG (51.9 %), and fimC (42.3 %). The most common genotype was plo/fimG/cbpA (17.3 %). Resistance to penicillin, erythromycin, and oxytetracycline was widespread, whereas all isolates remained susceptible to fluoroquinolones. Among antibiotic resistance genes, ermB (84.6 %) was the most prevalent, followed by tetM (57.7 %), dfrG (48.1 %), and blaZ (46.2 %). Eight isolates (15.4 %) exhibited multidrug resistance to five antibiotics. Notably, significant associations were observed between antibiotic resistance and virulence factor genes: cbpA with blaZ; fimG and cbpA with dfrG; fimG with tetM; and fimC with aph3-IIIa. These results suggest that this interaction may contribute to the pathogenicity of T. pyogenes. Our findings will provide valuable insights for the development of targeted strategies to control T. pyogenes infections.
化脓性true eperella pypygenes是在家畜和野生动物的皮肤和粘膜上发现的一种共生和机会性病原体。虽然化脓性乳杆菌在家畜中的临床意义已得到公认,但在韩国,关于这种病原体的信息很少。本研究旨在探讨化脓性肠杆菌临床感染分离株的毒力和耐药基因分布。一共52次 T。从韩国5个不同农场的患有呼吸窘迫或化脓性感染的牛身上分离出化脓菌。采用PCR检测毒力和耐药基因,采用纸片扩散法进行药敏试验。在毒力基因中,所有菌株均检出plo(100 %),其次是cbpA(65.4 %)、fimG(51.9 %)和fimC(42.3 %)。最常见的基因型为plo/ fig /cbpA(17.3% %)。对青霉素、红霉素和土霉素的耐药性普遍存在,而所有分离株仍对氟喹诺酮类药物敏感。抗生素耐药基因中以ermB(84.6 %)最多,其次是tetM(57.7 %)、dfrG(48.1 %)和blaZ(46.2 %)。8株(15.4 %)对5种抗生素耐多药。值得注意的是,抗生素耐药性与毒力因子基因之间存在显著相关性:cbpA与blaZ;g和cbpA与dfrG;g与tetM;c用ap3 - iiia。这些结果表明,这种相互作用可能有助于化脓性芽孢杆菌的致病性。我们的发现将为开发有针对性的控制化脓性肠杆菌感染的策略提供有价值的见解。
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引用次数: 0
Molecular survey on vector-borne pathogens in urban and peri-urban rodents in Spain 西班牙城市和城郊鼠类媒介传播病原体分子调查
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-16 DOI: 10.1016/j.vetmic.2025.110845
Jesús Barbero-Moyano , Moisés Gonzálvez , Javier Caballero-Gómez , Mariaelisa Carbonara , Mohamed Sh. Mohamud Yusuf , Remigio Martínez , Jairo Alfonso Mendoza-Roldán , Miguel Ángel Quevedo-Muñoz , Rafael Guerra , Pilar Soriano , Dietmar Crailsheim , Grazia Greco , Domenico Otranto , Ignacio García-Bocanegra
Rodents are key reservoirs and spillover hosts of major pathogens at the wildlife–domestic–human interface, playing a pivotal role in the eco-epidemiology of vector-borne diseases. Nevertheless, data on rodent infection by pathogens of animal and public health relevance remain limited, particularly in anthropized landscapes. This study aimed to evaluate the circulation of Leishmania infantum, Bartonella spp., and Hepatozoon spp. in rodent populations from anthropized areas in Spain, and to identify potential risk factors associated with infection by these pathogens. Spleen samples from 345 rodents—brown rats (Rattus norvegicus, n = 235), black rats (Rattus rattus, n = 62), and house mice (Mus musculus, n = 48)—collected throughout Spain were molecularly processed. Overall, 8.1 % (28/345; 95 % CI: 5.2–11.0) of rodents tested positive for at least one of the three pathogens. Leishmania infantum and Bartonella spp. were detected in 4.9 % and 3.2 % of the samples analysed, whereas Hepatozoon spp. infection was not detected. A significantly higher prevalence of L. infantum was found in house mice (12.5 %; P = 0.046; OR = 11.0) compared with black rats (1.6 %). Phylogenetic analysis of Bartonella spp. sequences revealed the presence of strains closely related to zoonotic species, particularly B. tribocorum, B. coopersplainsensis, B. rochalimae, and B. elizabethae. These findings indicate that rodents may contribute to the maintenance and transmission of some vector-borne zoonoses in anthropized areas of Spain, underscoring the need for strengthened surveillance and the implementation of control strategies to reduce the impact of rodent-borne pathogens on animal and public health.
啮齿动物是野生动物-家养动物-人类交界面主要病原体的主要宿主和外溢宿主,在媒介传播疾病的生态流行病学中起着关键作用。然而,与动物和公共卫生相关的病原体感染啮齿动物的数据仍然有限,特别是在人为化的景观中。本研究旨在评估西班牙人源化地区啮齿动物种群中婴儿利什曼原虫、巴尔通体和肝虫的传播情况,并确定与这些病原体感染相关的潜在危险因素。对西班牙各地采集的褐鼠(Rattus norvegicus, = 235)、黑鼠(Rattus Rattus, = 62)和家鼠(Mus musus, = 48)345份脾标本进行分子处理。总体而言,8.1 %(28/345;95 % CI: 5.2-11.0)的啮齿动物对三种病原体中的至少一种检测呈阳性。在4.9% %和3.2% %的分析样本中检出婴儿利什曼原虫和巴尔通体,而未检出肝虫感染。家鼠的婴儿乳杆菌患病率(12.5 %;P = 0.046;OR = 11.0)明显高于黑鼠(1.6 %)。巴尔通体序列的系统发育分析显示,巴尔通体与人畜共患病种密切相关,主要为tribocorum、B. coopersplainensis、B. rochalimae和B. elizabethae。这些发现表明,啮齿动物可能有助于西班牙人畜共患病地区一些媒介传播的人畜共患病的维持和传播,强调需要加强监测和实施控制战略,以减少啮齿动物传播的病原体对动物和公共卫生的影响。
{"title":"Molecular survey on vector-borne pathogens in urban and peri-urban rodents in Spain","authors":"Jesús Barbero-Moyano ,&nbsp;Moisés Gonzálvez ,&nbsp;Javier Caballero-Gómez ,&nbsp;Mariaelisa Carbonara ,&nbsp;Mohamed Sh. Mohamud Yusuf ,&nbsp;Remigio Martínez ,&nbsp;Jairo Alfonso Mendoza-Roldán ,&nbsp;Miguel Ángel Quevedo-Muñoz ,&nbsp;Rafael Guerra ,&nbsp;Pilar Soriano ,&nbsp;Dietmar Crailsheim ,&nbsp;Grazia Greco ,&nbsp;Domenico Otranto ,&nbsp;Ignacio García-Bocanegra","doi":"10.1016/j.vetmic.2025.110845","DOIUrl":"10.1016/j.vetmic.2025.110845","url":null,"abstract":"<div><div>Rodents are key reservoirs and spillover hosts of major pathogens at the wildlife–domestic–human interface, playing a pivotal role in the eco-epidemiology of vector-borne diseases. Nevertheless, data on rodent infection by pathogens of animal and public health relevance remain limited, particularly in anthropized landscapes. This study aimed to evaluate the circulation of <em>Leishmania infantum</em>, <em>Bartonella</em> spp., and <em>Hepatozoon</em> spp. in rodent populations from anthropized areas in Spain, and to identify potential risk factors associated with infection by these pathogens. Spleen samples from 345 rodents—brown rats (<em>Rattus norvegicus</em>, n = 235), black rats (<em>Rattus rattus</em>, n = 62), and house mice (<em>Mus musculus</em>, n = 48)—collected throughout Spain were molecularly processed. Overall, 8.1 % (28/345; 95 % CI: 5.2–11.0) of rodents tested positive for at least one of the three pathogens. <em>Leishmania infantum</em> and <em>Bartonella</em> spp. were detected in 4.9 % and 3.2 % of the samples analysed, whereas <em>Hepatozoon</em> spp. infection was not detected. A significantly higher prevalence of <em>L. infantum</em> was found in house mice (12.5 %; <em>P</em> = 0.046; OR = 11.0) compared with black rats (1.6 %). Phylogenetic analysis of <em>Bartonella</em> spp. sequences revealed the presence of strains closely related to zoonotic species, particularly <em>B. tribocorum</em>, <em>B. coopersplainsensis</em>, <em>B. rochalimae</em>, and <em>B. elizabethae</em>. These findings indicate that rodents may contribute to the maintenance and transmission of some vector-borne zoonoses in anthropized areas of Spain, underscoring the need for strengthened surveillance and the implementation of control strategies to reduce the impact of rodent-borne pathogens on animal and public health.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"312 ","pages":"Article 110845"},"PeriodicalIF":2.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790041","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
Mechanistic link between eIF4E phosphorylation and viral pathogenesis: Therapeutic insights from a porcine model eIF4E磷酸化与病毒发病机制之间的机制联系:来自猪模型的治疗见解
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-15 DOI: 10.1016/j.vetmic.2025.110818
Wen-Jun Tian , Yan-Ru Zhang , Jing-Ling You , Xiao-Jie Wu , Xiao-Fang Hu , Xiao-Jia Wang
Eukaryotic initiation factor 4E (eIF4E), a critical component of the host translational machinery, undergoes dynamic phosphorylation mediated by MNK kinases during viral infection, a process exploited by viruses to facilitate replication. To investigate the therapeutic potential of modulating this pathway, we established a sustained eIF4E hypophosphorylation model through pharmacological inhibition of MNK1/2 via eFT508 (15 mg/kg bw), a selective inhibitor. Oral administration of eFT508 significantly suppressed eIF4E phosphorylation across the piglet intestine and reduced viral replication of porcine epidemic diarrhea virus (PEDV). Furthermore, hypophosphorylation of eIF4E effectively restored antioxidant defenses by regulating the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) induced by arecoline treatment. eFT508 treatment also decreased oxidant levels and the production of proinflammatory cytokines, such as IL-6 and TNF-α, upon viral infection with PEDV. We subsequently conducted screening and functional verification via proteomic analysis, and the results revealed that eIF4E phosphorylation regulates downstream proteins, including inflammatory stress regulatory proteins such as TNFAIP3, and inflammatory factors such as NLRP3. These findings suggest that inhibitors targeting the MNK1/2-eIF4E axis confer tissue homeostasis and protection through coordinated anti-inflammatory and antioxidant effects. This work not only elucidates a druggable host factor in virus pathogenesis but also provides preclinical evidence for repurposing eFT508-class compounds in antiviral therapy and livestock resilience enhancement.
真核起始因子4E (Eukaryotic initiation factor 4E, eIF4E)是宿主翻译机制的一个重要组成部分,在病毒感染过程中,MNK激酶介导了真核起始因子4E的动态磷酸化,这一过程被病毒利用来促进复制。为了研究调节这一途径的治疗潜力,我们通过选择性抑制剂eFT508(15 mg/kg bw)对MNK1/2进行药理抑制,建立了持续的eIF4E低磷酸化模型。口服eFT508可显著抑制仔猪肠内eIF4E磷酸化,减少猪流行性腹泻病毒(PEDV)的病毒复制。此外,eIF4E的低磷酸化可通过调节花生碱诱导的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)水平,有效恢复抗氧化防御能力。eFT508治疗还降低了PEDV病毒感染后的氧化剂水平和促炎细胞因子(如IL-6和TNF-α)的产生。我们随后通过蛋白质组学分析进行筛选和功能验证,结果显示eIF4E磷酸化调节下游蛋白,包括炎症应激调节蛋白TNFAIP3和炎症因子NLRP3。这些发现表明,靶向MNK1/2-eIF4E轴的抑制剂通过协同抗炎和抗氧化作用赋予组织稳态和保护作用。这项工作不仅阐明了病毒发病机制中的可药物宿主因子,而且为重新利用eft508类化合物用于抗病毒治疗和增强牲畜的抗疫能力提供了临床前证据。
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引用次数: 0
Omaciclovir suppresses influenza A virus replication via interaction with viral PA protein 奥马昔洛韦通过与病毒PA蛋白相互作用抑制甲型流感病毒复制。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-14 DOI: 10.1016/j.vetmic.2025.110843
Changjie Lv , Wanxin Wei , Jianmei Wu , Shuang Wang , Guijie Guo
Influenza A virus (IAV) is a segmented negative-strand RNA virus that causes seasonal epidemics and occasional pandemics, posing a great threat to the public health. Current vaccines and antiviral drugs can not completely protect human and animals from IAV infection due to high frequency mutations in the viral genome and the emergence of drug-resistant strains, presenting an urgent need to explore new drugs against IAV infection. Here, we identified that omaciclovir significantly suppressed the replication of IAV. In vitro studies showed that omaciclovir inhibited replication of different IAV subtypes, including H1N1, H3N2 and H9N2. Furthermore, we demonstrated that omaciclovir strikingly attenuated replication of IAV in mice, as evidenced by a lower degree of tissue injury, slower body weight loss, and better survival, than the untreated animals following IAV infection. Mechanistically, omaciclovir interacted with viral PA protein, and interfered with the activity of IAV polymerase complexes, thereby limiting the synthesis of viral RNA (vRNA), complementary RNA (cRNA), and messenger RNA (mRNA). Together, these findings characterize the antiviral property of omaciclovir against IAV in vitro and in vivo, and provide insights into the development of potential antivirals against IAV infection.
甲型流感病毒(IAV)是一种分节负链RNA病毒,可引起季节性流行和偶发性大流行,对公众健康构成重大威胁。由于病毒基因组的高频突变和耐药菌株的出现,目前的疫苗和抗病毒药物不能完全保护人类和动物免受IAV感染,迫切需要探索抗IAV感染的新药。在这里,我们发现奥马昔洛韦显著抑制IAV的复制。体外研究表明,奥马昔洛韦可抑制不同IAV亚型的复制,包括H1N1、H3N2和H9N2。此外,我们证明了奥马昔洛韦显著地减弱了IAV在小鼠体内的复制,这证明了在IAV感染后,与未治疗的动物相比,组织损伤程度更低,体重减轻速度更慢,存活率更高。机制上,奥马昔洛韦与病毒PA蛋白相互作用,干扰IAV聚合酶复合物的活性,从而限制病毒RNA (vRNA)、互补RNA (cRNA)和信使RNA (mRNA)的合成。总之,这些发现表征了奥马昔洛韦在体外和体内对IAV的抗病毒特性,并为开发潜在的抗IAV感染的抗病毒药物提供了见解。
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引用次数: 0
A novel antiviral peptide Laby A1/A3 precursor-SUMO against PCV2 replication with broad-spectrum antiviral potential 具有广谱抗病毒潜力的抗PCV2复制的新型抗病毒肽Laby A1/A3前体- sumo
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-14 DOI: 10.1016/j.vetmic.2025.110842
Yan Zhang, Yuling Li, Qiqi Xia, Jingyuan Zhang, Yanmin Li, Long Zhou, Zijing Guo , Zhidong Zhang
Porcine circovirus type 2 (PCV2), the etiological agent of porcine circovirus-associated diseases (PCVAD), causes significant economic losses in swine production. In this study, the Labyrinthopeptin A1/A3 precursor-SUMO fusion (Laby A1/A3 precursor-SUMO), a novel therapeutic antiviral peptide, was successfully expressed and purified. The Laby A1/A3 precursor-SUMO was effective against PCV2 replication in the PK-15 cells in a concentration-dependent manner, as evidenced by significantly reduced viral Cap protein expression and DNA copy number. Notably, the peptide exhibited antiviral activity during co-treatment and post-treatment phases but not in pre-treatment. In vivo studies using PCV2-infected C57BL/6 mice confirmed its antiviral activity, as indicated by significantly reduced viral loads in the spleen. Mechanistically, the peptide counteracts PCV2-induced immunosuppression by restoring mRNA expression levels of type I interferons (IFN-α/β) and tumor necrosis factor-α (TNF-α) in infected cells. Furthermore, the Laby A1/A3 precursor-SUMO exhibited broad-spectrum antiviral activity of vesicular stomatitis virus (VSV), seneca valley virus (SVV), and porcine reproductive and respiratory syndrome virus (PRRSV) in a concentration-dependent manner. These findings establish Laby A1/A3 precursor-SUMO as a promising candidate for PCVAD therapy, with potential applications against multiple porcine pathogens.
猪圆环病毒2型(PCV2)是猪圆环病毒相关疾病(PCVAD)的病原,给养猪生产造成了重大的经济损失。本研究成功表达并纯化了迷宫肽A1/A3前体- sumo融合蛋白(Laby A1/A3前体- sumo)这一新型抗病毒治疗肽。Laby A1/A3前体- sumo在PK-15细胞中对PCV2复制具有浓度依赖性,这可以通过显著降低病毒Cap蛋白表达和DNA拷贝数来证明。值得注意的是,该肽在联合治疗和治疗后阶段表现出抗病毒活性,而在预处理阶段则没有。使用pcv2感染的C57BL/6小鼠进行的体内研究证实了其抗病毒活性,脾脏中的病毒载量显著降低。在机制上,该肽通过恢复感染细胞中I型干扰素(IFN-α/β)和肿瘤坏死因子-α (TNF-α)的mRNA表达水平来抵消pcv2诱导的免疫抑制。此外,Laby A1/A3前体- sumo对水疱性口炎病毒(VSV)、塞内卡谷病毒(SVV)和猪繁殖与呼吸综合征病毒(PRRSV)表现出广谱抗病毒活性,且呈浓度依赖性。这些发现表明,Laby A1/A3前体- sumo是一种有希望的PCVAD治疗候选药物,具有潜在的抗多种猪病原体的应用前景。
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引用次数: 0
Intranasal immunization of recombinant vaccinia virus bearing FeLV SU elicits systemic and mucosal immunity 携带FeLV SU的重组痘苗病毒鼻内免疫可引起全身和粘膜免疫。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-11 DOI: 10.1016/j.vetmic.2025.110841
Shan Zhan , Chenxiao Wei , Xin He , Yaoming Li
Feline leukemia virus (FeLV) is a major cause of mortality in domestic and wild felids, primarily spread through mucosal routes. Current FeLV vaccines offer moderate systemic protection but limited mucosal immunity. Previously, we showed that intranasal vaccination with a recombinant vaccinia virus (VV) can induce strong mucosal immune responses against multiple pathogens. Here, we constructed a recombinant VV expressing the surface unit (SU) of the FeLV envelope (VVFeLV-SU) and assessed its immunogenicity in a murine model following intranasal delivery. VVFeLV-SU was validated for FeLV SU expression and assessed replication kinetics in vitro. Intranasal immunization of BALB/c mice with VVFeLV-SU (1 ×107 PFU) induced humoral and cellular immune responses, including antibodies capable of neutralizing FeLV pseudovirus and FeLV SU-specific T cells producing IFN-γ, TNFα, and IL-4. Notably, mucosal secretory IgA specific to FeLV SU was also detectable after vaccination. Together, these results demonstrate that VVFeLV-SU has a favorable safety profile and moderate immunogenicity in mice, supporting further evaluation as a mucosal vaccine candidate against FeLV.
猫白血病病毒(FeLV)是家养和野生猫科动物死亡的主要原因,主要通过粘膜途径传播。目前的FeLV疫苗提供中等程度的全身保护,但粘膜免疫有限。先前,我们发现用重组痘苗病毒(VV)鼻内接种可以诱导针对多种病原体的强粘膜免疫反应。在这里,我们构建了表达FeLV包膜表面单位(SU)的重组VV (VVFeLV-SU),并在鼻内给药的小鼠模型中评估了其免疫原性。验证了VVFeLV-SU在体外表达FeLV-SU并评估了复制动力学。用VVFeLV-SU(1 ×107 PFU)鼻内免疫BALB/c小鼠可诱导体液和细胞免疫应答,包括能够中和FeLV假病毒和FeLV su特异性T细胞产生IFN-γ、TNFα和IL-4的抗体。值得注意的是,接种疫苗后也可检测到FeLV SU特异性的粘膜分泌IgA。总之,这些结果表明,VVFeLV-SU在小鼠中具有良好的安全性和适度的免疫原性,支持进一步评估作为FeLV的粘膜候选疫苗。
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引用次数: 0
From bias to reliable insight: Rethinking feature importance in microbiome analytics 从偏见到可靠的见解:重新思考微生物组分析中的特征重要性
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2025-12-11 DOI: 10.1016/j.vetmic.2025.110838
Souichi Oka , Kiyo Yoshida , Yoshiyasu Takefuji
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引用次数: 0
期刊
Veterinary microbiology
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