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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 Pub Date : 2026-02-01 Epub 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
Comparison of infection sequence of porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyorhinis to potentiate PRRSV-induced pneumonia 猪繁殖与呼吸综合征病毒(PRRSV)与缩耳支原体感染序列对PRRSV诱导肺炎增强作用的比较
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-05 DOI: 10.1016/j.vetmic.2025.110866
Jeongmin Suh, Sehyeong Ham, Hyejin Na, Ikjae Kang, Hyejean Cho, Chanhee Chae
The objective of this study was to evaluate the effect of infection sequence between Mycoplasma hyorhinis and porcine reproductive and respiratory syndrome virus (PRRSV). Thirty-six pigs were randomly allocated into six groups (six pigs per group) according to the order of infection: pigs inoculated first with M. hyorhinis followed by PRRSV (Mhr–PRRSV group), pigs co-inoculated simultaneously with both pathogens (PRRSV+Mhr group), pigs inoculated first with PRRSV followed by M. hyorhinis (PRRSV–Mhr group), pigs inoculated with either PRRSV or M. hyorhinis alone, and a negative control group. The Mhr–PRRSV, PRRSV+Mhr, and PRRSV–Mhr groups exhibited more severe clinical signs and a significant reduction in growth performance compared with the other three groups. These same groups also showed higher PRRSV loads in the blood, which corresponded with a greater severity of interstitial pneumonia. Furthermore, serum tumor necrosis factor-α concentrations were significantly elevated in these groups relative to the singly infected or control groups. The results of this study demonstrated that M. hyorhinis potentiates PRRSV-induced interstitial pneumonia in pigs, irrespective of infection sequence.
本研究的目的是评价猪鼻支原体与猪繁殖与呼吸综合征病毒(PRRSV)感染顺序的影响。36头猪按感染顺序随机分为6组,每组6头猪:先接种猪耳耳裂殖孔虫后再接种猪耳耳裂殖孔虫(Mhr-PRRSV组)、同时接种猪耳裂殖孔虫和猪耳裂殖孔虫(PRRSV+Mhr组)、先接种猪耳裂殖孔虫后再接种猪耳裂殖孔虫(PRRSV-Mhr组)、不接种猪耳裂殖孔虫或单独接种猪耳裂殖孔虫以及阴性对照组。与其他三组相比,mrh -PRRSV、PRRSV+Mhr和PRRSV-Mhr组表现出更严重的临床症状和显著的生长性能下降。这些人群血液中PRRSV的含量也较高,这与间质性肺炎的严重程度相对应。此外,血清肿瘤坏死因子-α浓度在这些组相对于单一感染或对照组显著升高。本研究结果表明,无论感染顺序如何,猪的缩鼻支原体都能增强prrsv诱导的间质性肺炎。
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引用次数: 0
Hemagglutinin-encoded mRNA vaccine confers efficient protection against H3N8 avian influenza virus in mice 血凝素编码mRNA疫苗对小鼠H3N8禽流感病毒具有有效的保护作用。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-21 DOI: 10.1016/j.vetmic.2025.110847
Jiayan Wu , Wenjie Jiang , Xingyao Guo , Jingwen Li , Shengnan Wang , Zhimin Wan , Quan Xie , Hongxia Shao , Wei Gao , Aijian Qin , Tuofan Li , Jianqiang Ye
Recently, the endemic of novel H3N8 avian influenza virus (AIV) in chickens poses significant threats to poultry industry and public health, driving the urgent need for safe and immunogenic vaccines. In this study, an mRNA vaccine, HA mRNA-LNP, expressing the hemagglutinin (HA) protein of H3N8 was developed. The sequence of HA of H3N8 was first codon-optimized and cloned into the pUC57 vector. The mRNA of the HA was synthesized by in vitro transcription (IVT) and enzymatic capping. The efficient expression of the HA protein of the mRNA was confirmed by Western blot, indirect immunofluorescence assay (IFA), and flow cytometry in 293 T or DF-1 cells. The mRNA vaccine was then encapsulated with lipid nanoparticle (LNP) named as HA mRNA-LNP. Furthermore, two doses of HA mRNA-LNP in mice through intramuscular vaccination elicited robust humoral immune response against H3N8, with peak hemagglutination inhibition (HI) and microneutralization (MN) titers reaching 1:5120 and 1:8192, respectively. This vaccine conferred efficient protection against the challenge of H3N8, evidenced by accelerated body weight recovery, undetectable viral loads in lung tissues, and milder pulmonary pathological changes. All these demonstrate that the HA mRNA-LNP vaccine generated here is a promising candidate for combating H3N8 infections.
近年来,新型H3N8禽流感病毒(AIV)在鸡群中的流行对家禽业和公众健康构成了重大威胁,迫切需要安全的免疫原性疫苗。本研究研制了一种表达H3N8血凝素(HA)蛋白的mRNA疫苗HA mRNA- lnp。首先对H3N8的HA序列进行密码子优化,克隆到pUC57载体上。通过体外转录(IVT)和酶盖法合成HA mRNA。Western blot、间接免疫荧光法(IFA)和流式细胞术在293 T或DF-1细胞中证实了HA蛋白的高效表达。然后用脂质纳米颗粒(LNP)包封mRNA疫苗,命名为HA mRNA-LNP。此外,通过肌肉注射两种剂量的HA mRNA-LNP,小鼠对H3N8产生了强大的体液免疫反应,血凝抑制(HI)和微中和(MN)的峰值滴度分别达到1:5120和1:8192。该疫苗可有效保护小鼠免受H3N8病毒的攻击,其表现为体重恢复加快、肺组织中检测不到病毒载量以及肺部病理改变较轻。所有这些都表明,这里产生的HA mRNA-LNP疫苗是对抗H3N8感染的有希望的候选疫苗。
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引用次数: 0
APOBEC3F restricts PRRSV replication through its CD2 domain and interaction with host antiviral proteins APOBEC3F通过其CD2结构域和与宿主抗病毒蛋白的相互作用来限制PRRSV的复制。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-02 DOI: 10.1016/j.vetmic.2026.110872
Pengcheng Wang, Xuan Hu, Lang Tian, Xiaoyu Lu, Qian Xiong, Kangli Liang, Qiaomu Deng, Guilan Wen, Anchun Cheng
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen that causes substantial economic losses to the global swine industry. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 F (APOBEC3F), a key constituent of cytoplasmic processing bodies (P-bodies) and a member of the deaminase protein family, possesses intrinsic antiviral activity. This study systematically investigates the effects of APOBEC3F and its functional domains on PRRSV replication. This study systematically investigated the effects of APOBEC3F and its functional domains on PRRSV replication. We found that overexpression of APOBEC3F and its C-terminal deaminase domain (CD2) markedly suppressed PRRSV replication (including transcription, protein expression, and viral titers) in susceptible porcine cells. Conversely, APOBEC3F knockdown enhanced viral replication. Notably, several PRRSV proteins—NSP1α, NSP1β, NSP5, NSP7, GP4, GP5, and N—were found to downregulate endogenous APOBEC3F mRNA expression in host cells. Moreover, IP-MS analysis identified several potential candidate interactors, including DEAD-box helicases (such as DDX6 and MOV10) and other host factors, suggesting that APOBEC3F may associate with P-body components to exert its antiviral function. These results offer new insights into the molecular mechanisms of APOBEC3F-mediated antiviral defense against PRRSV and underscore its potential as a therapeutic target.
猪繁殖与呼吸综合征病毒(PRRSV)是给全球养猪业造成重大经济损失的主要病原体。载脂蛋白B mrna编辑酶催化多肽样3 F (APOBEC3F)是细胞质加工体(P-bodies)的关键成分,也是脱胺酶蛋白家族的成员,具有内在的抗病毒活性。本研究系统地探讨了APOBEC3F及其功能域对PRRSV复制的影响。本研究系统地探讨了APOBEC3F及其功能域对PRRSV复制的影响。我们发现APOBEC3F及其c端脱氨酶结构域(CD2)的过表达显著抑制PRRSV在易感猪细胞中的复制(包括转录、蛋白表达和病毒滴度)。相反,敲低APOBEC3F可增强病毒复制。值得注意的是,几种PRRSV蛋白(nsp1 α、NSP1β、NSP5、NSP7、GP4、GP5和n)在宿主细胞中下调内源性APOBEC3F mRNA的表达。此外,IP-MS分析发现了几种潜在的候选相互作用物,包括DEAD-box解旋酶(如DDX6和MOV10)和其他宿主因子,表明APOBEC3F可能与p体成分结合发挥其抗病毒功能。这些结果为apobec3f介导的PRRSV抗病毒防御的分子机制提供了新的见解,并强调了其作为治疗靶点的潜力。
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引用次数: 0
The disruption of two putative peptidases affects the extracellular proteolytic and metabolic activity of Mycoplasma bovis 两种假定的肽酶的破坏影响了牛支原体的细胞外蛋白水解和代谢活性。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-01 DOI: 10.1016/j.vetmic.2025.110856
Shijie Geng , Dilhani Ekanayake , Anna Kanci Condello , David P. De Souza , Sheik Nadeem Elahee Doomun , Chintha K. Premachandre , Jordi Hondrogiannis , Glenn F. Browning , Sara M. Klose , Kelly A. Tivendale , Nadeeka K. Wawegama
Although proteolytic activity has been shown to be critical for virulence in mycoplasmas, the role of this activity in the pathogenesis of infections with Mycoplasma bovis is yet to be fully elucidated. Two putative peptidase genes (MBOVPG45_0176 and MBOVPG45_0685) of M. bovis were previously shown to be required for the survival of the organism in association with host cells. To investigate the metabolic functions of the two genes, proteolytic screening of M. bovis cell-associated and secreted proteins, together with metabolomic profiling by gas chromatography-mass spectrometry (GC-MS), were used in this study to compare mutants in which the genes were disrupted by a transposon with their parent strain. Cloning and expression of the two genes were also attempted to study their enzymatic activity. Zymography using different peptidase substrates detected secreted proteins of M. bovis with proteolytic activity against gelatin and collagen. Although peptidase activity was reduced in the mutant in which the MBOVPG45_0176 gene was disrupted, the expressed glutathione S-transferase-tagged recombinant product of this gene had no detectable proteolytic activity, possibly due to the absence of propeptide cleavage required for peptidase maturation. Comparative metabolomic profiling revealed that mutants with either of these genes disrupted had significantly lower abundances of amino acids, nucleoside metabolites, and glycolytic intermediates. These results suggest the two putative peptidase genes have a role in metabolic and extracellular proteolytic activity of M. bovis, although further investigation is needed to determine the targets of the proteolytic activity of their products and their precise role in host-mycoplasma interactions.
虽然蛋白水解活性已被证明对支原体的毒力至关重要,但这种活性在牛支原体感染的发病机制中的作用尚未完全阐明。两个假定的肽酶基因(MBOVPG45_0176和MBOVPG45_0685)先前被证明是与宿主细胞相关的生物体存活所必需的。为了研究这两个基因的代谢功能,本研究使用了牛分枝杆菌细胞相关蛋白和分泌蛋白的蛋白水解筛选,以及气相色谱-质谱(GC-MS)的代谢组学分析,将基因被转座子破坏的突变体与其亲本菌株进行了比较。并对这两个基因的克隆和表达进行了研究。利用不同的肽酶底物酶谱法检测牛分枝杆菌分泌的蛋白对明胶和胶原蛋白具有水解活性。虽然在MBOVPG45_0176基因被破坏的突变体中,肽酶活性降低,但表达的谷胱甘肽s -转移酶标记的重组产物没有检测到蛋白水解活性,可能是由于缺乏肽酶成熟所需的前肽裂解。比较代谢组学分析显示,这些基因中任何一个被破坏的突变体氨基酸、核苷代谢物和糖酵解中间体的丰度显著降低。这些结果表明,这两个假定的肽酶基因在牛支原体的代谢和细胞外蛋白水解活性中起作用,尽管需要进一步的研究来确定它们产物的蛋白水解活性的目标和它们在宿主-支原体相互作用中的确切作用。
{"title":"The disruption of two putative peptidases affects the extracellular proteolytic and metabolic activity of Mycoplasma bovis","authors":"Shijie Geng ,&nbsp;Dilhani Ekanayake ,&nbsp;Anna Kanci Condello ,&nbsp;David P. De Souza ,&nbsp;Sheik Nadeem Elahee Doomun ,&nbsp;Chintha K. Premachandre ,&nbsp;Jordi Hondrogiannis ,&nbsp;Glenn F. Browning ,&nbsp;Sara M. Klose ,&nbsp;Kelly A. Tivendale ,&nbsp;Nadeeka K. Wawegama","doi":"10.1016/j.vetmic.2025.110856","DOIUrl":"10.1016/j.vetmic.2025.110856","url":null,"abstract":"<div><div>Although proteolytic activity has been shown to be critical for virulence in mycoplasmas, the role of this activity in the pathogenesis of infections with <em>Mycoplasma bovis</em> is yet to be fully elucidated. Two putative peptidase genes (MBOVPG45_0176 and MBOVPG45_0685) of <em>M. bovis</em> were previously shown to be required for the survival of the organism in association with host cells. To investigate the metabolic functions of the two genes, proteolytic screening of <em>M. bovis</em> cell-associated and secreted proteins, together with metabolomic profiling by gas chromatography-mass spectrometry (GC-MS), were used in this study to compare mutants in which the genes were disrupted by a transposon with their parent strain. Cloning and expression of the two genes were also attempted to study their enzymatic activity. Zymography using different peptidase substrates detected secreted proteins of <em>M. bovis</em> with proteolytic activity against gelatin and collagen. Although peptidase activity was reduced in the mutant in which the MBOVPG45_0176 gene was disrupted, the expressed glutathione S-transferase-tagged recombinant product of this gene had no detectable proteolytic activity, possibly due to the absence of propeptide cleavage required for peptidase maturation. Comparative metabolomic profiling revealed that mutants with either of these genes disrupted had significantly lower abundances of amino acids, nucleoside metabolites, and glycolytic intermediates. These results suggest the two putative peptidase genes have a role in metabolic and extracellular proteolytic activity of <em>M. bovis</em>, although further investigation is needed to determine the targets of the proteolytic activity of their products and their precise role in host-mycoplasma interactions.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"313 ","pages":"Article 110856"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918488","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
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 Pub Date : 2026-02-01 Epub 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
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 : 2026-02-01 Epub 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
Identification of novel B-cell neutralizing epitopes in goose Astrovirus type 2 鹅星状病毒2型新b细胞中和表位的鉴定。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.vetmic.2026.110874
Shichao Yuan , Rui Fu , Bangfeng Xu , Wenqing Wang , Huamao Ding , Xue Pan , Chunxiu Yuan , Qinfang Liu , Zhifei Zhang , Qiaoyang Teng , Xiaona Shi , Minghao Yan , Peirong Jiao , Dawei Yan , Zejun Li
Since 2015, outbreaks of goose Astrovirus type 2 (GAstV-2) have caused significant economic losses in the goose industry by inducing severe visceral and articular gout in goslings, with mortality rates reaching up to 50 %. The capsid (Cap) protein of GAstV-2 is the primary structural protein that elicits immune responses, but it has not been extensively studied for neutralizing epitopes or infection mechanisms. In this study, two novel neutralizing monoclonal antibodies (mAbs) 4A7 and 8H3 were generated, which specifically target the Cap protein and effectively inhibit GAstV-2 infection in vitro. Epitope mapping using alanine-scanning mutagenesis revealed that the epitopes recognized by mAbs 4A7 and 8H3 are located within the amino acids sequences 443ESCSFLVF450 and 425QVTPSLVYNF434 of the Cap protein, respectively. These two epitopes are highly conserved among GAstV-2 strains, but show substantial divergence from GAstV-1 strains. Structural analysis indicated that these epitopes are situated on the surface of the Cap protein, within the P2 domain, which is critical for virus-receptor interactions and immune recognition. The findings not only identify novel neutralizing epitopes in GAstV-2 but also highlight the potential of mAbs 4A7 and 8H3 for developing epitope-based vaccines and diagnostic assays.
自2015年以来,鹅星状病毒2型(GAstV-2)的爆发引发了鹅雏严重的内脏和关节痛风,给鹅业造成了重大经济损失,死亡率高达50% %。GAstV-2的衣壳蛋白(Cap)是引发免疫应答的主要结构蛋白,但尚未对其中和表位或感染机制进行广泛研究。本研究制备了两种新的中和性单克隆抗体(mab) 4A7和8H3,特异性靶向Cap蛋白,在体外有效抑制GAstV-2感染。利用丙氨酸扫描诱变技术进行表位定位发现,单克隆抗体4A7和8H3识别的表位分别位于Cap蛋白的443ESCSFLVF450和425QVTPSLVYNF434氨基酸序列内。这两个表位在GAstV-2株中高度保守,但与GAstV-1株存在较大差异。结构分析表明,这些表位位于Cap蛋白表面的P2结构域内,该结构域对病毒-受体相互作用和免疫识别至关重要。这些发现不仅在GAstV-2中发现了新的中和表位,而且强调了单克隆抗体4A7和8H3在开发基于表位的疫苗和诊断分析方面的潜力。
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引用次数: 0
Prodigiosin targeting alveolar macrophages to mitigate the inflammatory response induced by H9N2 viral infection Prodigiosin靶向肺泡巨噬细胞减轻H9N2病毒感染诱导的炎症反应
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-08 DOI: 10.1016/j.vetmic.2025.110824
Jian Xu , Leyu Tao , Mengfei Zhang , Shuying Zhang , Zhihua Tang
Respiratory viruses continue to present serious public health challenges. Alveolar macrophages (AMs) serve a frontline role in antiviral defense. Nevertheless, dysregulated inflammatory responses contribute to pulmonary damage. Recent research has highlighted the immunomodulatory properties of prodigiosin (PDN), particularly its capacity to fine-tune innate immune activity in response to pathogenic insults. PDN has been shown to modulate inflammatory responses, thereby attenuating tissue injury and promoting recovery. However, whether these protective effects are mediated specifically through the regulation of alveolar macrophages during respiratory viral infections remains to be elucidated. In this study, we show that PDN significantly alleviates both morbidity and mortality in a mouse model of H9N2 AIV infection. PDN leads to a substantial decline in pro-inflammatory cytokine production, mitigates histopathological lung damage. Mechanistically, PDN downregulates the Wnt/β-catenin pathway while preserving mitochondrial function. Furthermore, PDN inhibits the senescent state of AMs in aging mice. Therefore, our findings indicate that PDN alleviates inflammation and lung injury from respiratory viral infections by acting on AM, thereby highlighting its therapeutic potential for viral pneumonia, especially in the elderly.
呼吸道病毒继续构成严重的公共卫生挑战。肺泡巨噬细胞(AMs)在抗病毒防御中起着一线作用。然而,炎症反应失调会导致肺损伤。最近的研究强调了prodigisin (PDN)的免疫调节特性,特别是其在应对致病性损伤时微调先天免疫活性的能力。PDN已被证明可以调节炎症反应,从而减轻组织损伤并促进恢复。然而,这些保护作用是否通过呼吸道病毒感染期间肺泡巨噬细胞的调节特异性介导仍有待阐明。在这项研究中,我们发现PDN显著减轻了H9N2 AIV感染小鼠模型的发病率和死亡率。PDN导致促炎细胞因子的产生大幅下降,减轻组织病理学肺损伤。在机制上,PDN下调Wnt/β-catenin通路,同时保持线粒体功能。此外,PDN抑制衰老小鼠AMs的衰老状态。因此,我们的研究结果表明,PDN通过作用于AM减轻呼吸道病毒感染引起的炎症和肺损伤,从而突出了其治疗病毒性肺炎的潜力,特别是在老年人中。
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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 Pub Date : 2026-02-01 Epub 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。
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引用次数: 0
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Veterinary microbiology
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