Microbial pathogenesis最新文献_第10页

A review of the role of graphene-based nanomaterials in tackling challenges posed by the COVID-19 pandemic 综述石墨烯基纳米材料在应对 COVID-19 大流行带来的挑战中的作用。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-22 DOI: 10.1016/j.micpath.2024.107059

Sachin Sharma Ashok Kumar , Shahid Bashir , M. Pershaanaa , Fathiah Kamarulazam , A.V. Kuppusamy , Nujud Badawi , K. Ramesh , S. Ramesh

In 2020, the World Health Organization (WHO) declared a pandemic due to the emergence of the coronavirus disease (COVID-19) which had resulted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At present, the emergence of many new variants and mutants were found to be more harmful compared to the previous strains. As a result, research scientists around the world had devoted significant efforts to understand the mechanism, causes and transmission due to COVID-19 along with the treatment to cure these diseases. However, despite achieving several findings, much more was unknown and yet to be explored. Hence, along with these developments, it is also extremely essential to design effective systems by incorporating smart materials to battle the COVID-19. Therefore, several approaches have been implemented to combat against COVID-19. Recently, the graphene-based materials have been explored for the current COVID-19 and future pandemics due to its superior physicochemical properties, providing efficient nanoplatforms for optical and electrochemical sensing and diagnostic applications with high sensitivity and selectivity. Moreover, based on the photothermal effects or reactive oxygen species formation, the carbon-based nanomaterials have shown its potentiality for targeted antiviral drug delivery and the inhibitory effects against pathogenic viruses. Therefore, this review article sheds light on the recent progress and the most promising strategies related to graphene and related materials and its applications for detection, decontamination, diagnosis, and protection against COVID-19. In addition, the key challenges and future directives are discussed in detail for fundamental design and development of technologies based on graphene-based materials along with the demand aspects of graphene-based products and lastly, our personal opinions on the appropriate approaches to improve these technologies respectively.

2020 年，由于严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）导致冠状病毒病（COVID-19）的出现，世界卫生组织（WHO）宣布该病为大流行病。目前，许多新变种和变异株的出现被认为比以前的毒株危害更大。因此，世界各地的科研人员都在努力研究 COVID-19 的发病机制、原因、传播途径以及治疗方法。然而，尽管取得了一些研究成果，但仍有许多未知因素有待探索。因此，在取得这些进展的同时，还必须设计出有效的系统，结合智能材料来对抗 COVID-19。因此，人们采用了多种方法来对抗 COVID-19。最近，石墨烯基材料因其优越的物理化学特性，为高灵敏度和高选择性的光学、电化学传感和诊断应用提供了高效的纳米平台，因此已被探索用于应对当前的 COVID-19 和未来的流行病。此外，基于光热效应或活性氧的形成，碳基纳米材料在靶向抗病毒给药和抑制致病病毒方面也显示出了潜力。因此，这篇综述文章揭示了与石墨烯和相关材料有关的最新进展和最有前景的策略，以及其在检测、净化、诊断和防护 COVID-19 方面的应用。此外，文章还详细讨论了基于石墨烯材料的技术的基础设计和开发所面临的主要挑战和未来方向，以及石墨烯产品的需求方面，最后还就改进这些技术的适当方法分别提出了我们的个人观点。

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引用次数: 0

Inhibitory activity of Euterpe oleracea Mart. fruit extract in West Nile virus infection Euterpe oleracea Mart.果实提取物对西尼罗河病毒感染的抑制活性。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-22 DOI: 10.1016/j.micpath.2024.107075

Bruna N. Teixeira , Fabiana P. Albernaz , Andréa C. Oliveira , Andre Marco O. Gomes , Valéria L. Carvalho , Carlos Alberto M. Carvalho

West Nile virus (WNV) is a neurovirulent arbovirus whose epidemic capacity is enhanced by the wide occurrence of competent vectors and susceptible avian amplifying hosts. In this study, we investigated the antiviral potential of Euterpe oleracea Mart. fruit extract (EoFE) in WNV infection of monkey kidney (Vero) cell cultures. A chromatographic authentication of the extract revealed a typical two-peak fingerprint attributable to the major anthocyanins of the fruit. As assessed by plaque assays in Vero cells, the extract showed a significant concentration-dependent antiviral effect when present throughout the infection procedure, reaching a maximum inhibition of 66.8 % at 2 mg/mL without significant cytotoxicity or direct action on virus particles. A time-of-addition assay revealed that this anti-WNV effect was mostly exerted after virus entry, as incubation of Vero cells with EoFE before or during virus addition resulted in a nonsignificant decrease of infection efficiency. These results demonstrated a promising potential of EoFE in inhibiting WNV infection that can be further explored as an antiviral strategy.

西尼罗河病毒（WNV）是一种神经病毒性虫媒病毒，其流行能力因有能力的载体和易感禽类扩增宿主的广泛存在而增强。在这项研究中，我们研究了Euterpe oleracea Mart.果实提取物（EoFE）在猴肾（Vero）细胞培养物感染WNV时的抗病毒潜力。提取物的色谱鉴定显示了典型的双峰指纹图谱，这归因于果实中的主要花青素。通过在 Vero 细胞中进行斑块检测，该提取物在整个感染过程中都显示出显著的浓度依赖性抗病毒效果，在 2 mg/mL 浓度下的最大抑制率为 66.8%，但没有明显的细胞毒性或对病毒颗粒的直接作用。添加时间测定显示，这种抗 WNV 作用主要是在病毒进入后产生的，因为在病毒添加前或添加过程中用 EoFE 培养 Vero 细胞会导致感染效率无明显下降。这些结果表明，EoFE 在抑制 WNV 感染方面具有广阔的潜力，可作为一种抗病毒策略进行进一步探索。

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引用次数: 0

Dietary administration of Bacillus amyloliquefaciens AV5 on antioxidant activity, blood parameters, and stress responses of Nile tilapia (Oreochromis niloticus) raised under hypoxia and temperature variability 在缺氧和温度变化条件下膳食添加淀粉样芽孢杆菌 AV5 对尼罗罗非鱼（Oreochromis niloticus）抗氧化活性、血液参数和应激反应的影响。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-22 DOI: 10.1016/j.micpath.2024.107067

Vicent Michael Shija , Glory Emanuel Zakaria , Kwaku Amoah , Yi Li , Fortunatus Masanja , Yong Zhong , Xiaopiao Zhong , Jia Cai

The ability of Nile tilapia to tolerate hypoxia, as well as low and high temperatures, presents a significant economic concern, as it adversely affects their growth and leads to increased mortality rates. A 42-day feeding trial was conducted to evaluate the impact of adding Bacillus amyloliquefaciens AV5 to a fish meal on the physiological response of Nile tilapia. Three meals were administered to fish (23.4 ± 0.3g) in triplicates. The diets included GC (without B. amyloliquefaciens AV5), G1 (10⁶ cfu/g), and G2 (10⁸ cfu/g). After the treatment trial, we assessed the antioxidant parameters, hemato-immunological indices, and stress-related genes in O. niloticus. Subsequently, we subjected the fish to hypoxia for 20h and low and high temperatures for 3h each. The findings demonstrated a significant rise in white blood cells, red blood cells, haemoglobin, and hematocrit levels in the blood of fish that were fed a meal supplemented with B. amyloliquefaciens AV5, compared to the control group (GC) (P<0.05), the serum of all fish groups that were supplemented with B. amyloliquefaciens AV5 exhibited an increase in catalase, total antioxidant capacity and superoxide dismutase activity and a decrease in lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, pyruvate kinase, myeloperoxidase, glucose, cortisol (P < 0.05). In addition, all fish diet groups that received B. amyloliquefaciens AV5 as a supplement exhibited elevated levels of HIF-1α and HSP70 expression in their livers (P<0.05). Nile tilapia in the G2 diet, exhibited improved values in most evaluated indices under various stress settings (P<0.05). These data indicate that the G2 supplement may be used as a preventive measure to weaken the impacts of environmental stress on O. niloticus.

尼罗罗非鱼无法耐受缺氧以及低温和高温，这对其生长造成了不利影响，并导致死亡率上升，因而引发了重大的经济问题。为了评估在鱼餐中添加淀粉芽孢杆菌 AV5 对尼罗罗非鱼生理反应的影响，我们进行了一项为期 42 天的喂养试验。对鱼（23.4 ± 0.3 克）进行了三餐喂养，每餐三份。日粮包括 GC（不含淀粉芽孢杆菌 AV5）、G1（106cfu/g）和 G2（108cfu/g）。处理试验结束后，我们评估了黑线鳕的抗氧化参数、血液免疫指数和应激相关基因。随后，我们将鱼置于缺氧环境 20 小时，低温和高温环境各 3 小时。研究结果表明，与对照组（GC）相比，喂食添加了淀粉芽孢杆菌 AV5 的鱼血液中的白细胞、红细胞、血红蛋白和血细胞比容水平明显升高（P

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引用次数: 0

Inhibitory effect of Bacillus velezensis 1273 strain cell-free supernatant against developing and preformed biofilms of Staphylococcus aureus and MRSA 枯草芽孢杆菌 1273 菌株无细胞上清液对金黄色葡萄球菌和 MRSA 正在形成和已经形成的生物膜的抑制作用。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-22 DOI: 10.1016/j.micpath.2024.107065

Hugo Felix Perini , Bianca de Barros Pereira , Eduarda Guimarães Sousa , Beatriz Sodré Matos , Ligia Carolina da Silva Prado , Vasco Ariston de Carvalho Azevedo , Siomar de Castro Soares , Marcos Vinicius da Silva

Microbial biofilms constitute a significant virulence factor and a substantial challenge in clinical environments due to their role in promoting antimicrobial resistance and their resilience to eradication efforts. Methicillin-resistant Staphylococcus aureus (MRSA) infections substantially increase healthcare costs, extend hospitalizations, and elevate morbidity and mortality rates. Therefore, developing innovative strategies to target and eliminate these bacteria and their biofilms effectively is imperative for robust epidemiological control. In this study, we evaluated the antibacterial and antibiofilm activities of cell-free supernatant (CFS) obtained from the Bacillus velezensis 1273 strain culture. Our data showed that CFS inhibited the growth of S. aureus ATCC 29213 and MRSA (clinical strain), with greater efficacy observed against S. aureus (1:16 dilution). Furthermore, CFS showed substantial potential in reducing biofilm formation in both strains (∼30 %) at subinhibitory concentrations. Additionally, the antibacterial activity against biofilm-formed cells showed that pure CFS treatment decreased the viability of S. aureus (60 %) and MRSA (45 %) sessile cells. We further demonstrated that CFS treatment induces the production of reactive oxygen species (ROS) and damages the membranes and cell walls of the pathogen cells. Genome analysis revealed the presence of genes encoding bacteriocins and secondary metabolites with antibacterial activity in the B. velezensis 1273 genome. These findings highlight the potential of probiotic bacterial metabolites as antibiofilm and anti-multidrug-resistant pathogens.

微生物生物膜是一个重要的致病因素，也是临床环境中的一个重大挑战，因为它们在促进抗菌药耐药性方面起着重要作用，而且对根除工作具有很强的抵御能力。耐甲氧西林金黄色葡萄球菌（MRSA）感染大大增加了医疗成本，延长了住院时间，提高了发病率和死亡率。因此，要想有效控制流行病，就必须制定创新策略，针对并消除这些细菌及其生物膜。在这项研究中，我们评估了从 Velezensis 杆菌 1273 菌株培养物中获得的无细胞上清液（CFS）的抗菌和抗生物膜活性。我们的数据显示，CFS 可抑制金黄色葡萄球菌 ATCC 29213 和 MRSA（临床菌株）的生长，其中对金黄色葡萄球菌（1:16 稀释度）的效果更好。此外，在亚抑制浓度下，CFS 在减少这两种菌株的生物膜形成方面表现出了巨大的潜力（∼30%）。此外，针对生物膜形成细胞的抗菌活性表明，纯 CFS 处理可降低金黄色葡萄球菌（60%）和 MRSA（45%）无柄细胞的存活率。我们进一步证实，CFS 处理会诱导活性氧（ROS）的产生，并破坏病原体细胞的膜和细胞壁。基因组分析表明，在 B. velezensis 1273 基因组中存在编码细菌素和具有抗菌活性的次级代谢产物的基因。这些发现凸显了益生菌代谢物作为抗生物膜和抗多重耐药病原体的潜力。

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引用次数: 0

The treatment of Enterococcus faecalis related root canal biofilms with phage therapy 用噬菌体疗法治疗与粪肠球菌有关的根管生物膜。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-22 DOI: 10.1016/j.micpath.2024.107081

Hilal Basak Erol , Banu Kaskatepe , Damla Gocmen , Fatma Gul Ziraman

As one of the global concerns, antimicrobial resistance crisis increases the clinical importance of Enterococcus species. Enterococcus faecalis (E. faecalis) specifically penetrates the dentinal tubules and remains prevalent even after endodontic treatment. It has also biofilm forming character as well as the development of resistance to antibiotics. Sodium hypochlorite (NaOCl) is considered the gold standard among antibacterial washing solutions. However, due to its toxic effects, its usage limitations have led to the search for natural, non-toxic alternatives. Phages can be considered an important alternative because of their effects on specific bacteria. The objective of this study was to compare the effect of isolated active vB_Ef1 phage on the removal of E. faecalis biofilm in dentin, together and separately with the chemical irrigation solution NaOCl. As a result of study, the optimal NaOCl solution concentration to be applied with vB_Ef1 phage is 0.5 %, and the use of solution at this value reduces the biofilm mass by 84 %, reaching the highest biofilm mass reduction value. It was found that the combination of phage and NaOCl at appropriate concentrations had the strongest biofilm disruption effect.

作为全球关注的问题之一，抗菌药耐药性危机增加了肠球菌的临床重要性。粪肠球菌（E. faecalis）能特异性地穿透牙本质小管，甚至在牙髓治疗后仍然普遍存在。它还具有形成生物膜的特性，并对抗生素产生抗药性。次氯酸钠（NaOCl）被认为是抗菌清洗液中的黄金标准。然而，由于次氯酸钠的毒性作用，其使用限制导致人们开始寻找天然、无毒的替代品。噬菌体因其对特定细菌的作用而被认为是一种重要的替代品。本研究的目的是比较分离出的活性 vB_Ef1 噬菌体与化学灌洗液 NaOCl 一起和单独使用对去除牙本质中的粪大肠杆菌生物膜的效果。研究结果表明，与 vB_Ef1 噬菌体一起使用的最佳 NaOCl 溶液浓度为 0.5%，使用该浓度的溶液可使生物膜质量减少 84%，达到生物膜质量减少的最高值。研究发现，噬菌体和适当浓度的 NaOCl 的组合具有最强的生物膜破坏效果。

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引用次数: 0

Isolation and evaluation of bacteriophage cocktail for the control of colistin-resistant Escherichia coli 用于控制耐大肠菌素大肠埃希氏菌的噬菌体鸡尾酒的分离和评估。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-21 DOI: 10.1016/j.micpath.2024.107056

Xiaolin Zhu , Tianshi Xiao , Xuchen Jia , Xuan Ni , Xiaosong Zhang , Yizhuo Fang , Zhihui Hao

The frequent emergence of colistin-resistant E. coli worldwide drives the exploration of alternative therapies, and bacteriophages (phages) have emerged as promising candidates to tackle this challenge. In this study, three E. coli phages were isolated, screened, and evaluated against 96 colistin-resistant strains obtained from diverse sources. The combined recognition rate for these strains was 43.6 %, while individually it ranged from 17.0 % to 24.5 %. Notably, among the tested phages (FJ3-79, SD1-92L, and FJ4-63), FJ4-63 demonstrated exceptional characteristics in regulating host population dynamics upon infection by exhibiting a shorter latent period (20 min) and a larger burst size (95.99 ± 3.61 PFU/cell). Furthermore, it exhibited relative stability at pH 3–11 and below 60 °C. Transmission electron microscopy and genomic analysis classified phage FJ4-63 belongs to the Dhakavirus genus within the Straboviridae family. Its genome comprised a linear double-stranded DNA measuring 169,669 bp (containing 272 coding sequences) with a GC content of 39.76 %, of which 93 (34.2 %) had known functions, and the remaining 177 were annotated as hypothetical proteins. Additionally, two tRNAs were recognized, possess the “holin-endolysin” lytic system, and no resistance or virulence genes were detected. The phylogenetic tree and average nucleotide identity (ANI) analysis revealed that phage FJ4-63 exhibited the highest similarity to Escherichia phage C6 (679410.1), indicating a consistent close relationship within the same branch. The cocktail comprising three phages exhibits enhanced in vitro bactericidal efficacy compared to a single phage. At high doses with MOI = 100, it rapidly and completely eradicates bacteria within 1 h while significantly reducing bacterial biofilms. All this evidence suggests that lytic phages offer an effective solution for clinical treatment, with a phage cocktail demonstrating greater potential in the alternative management of colistin-resistant E. coli infections.

全球频繁出现耐大肠菌素的大肠杆菌，促使人们探索替代疗法，而噬菌体（噬菌体）已成为应对这一挑战的有希望的候选疗法。本研究分离、筛选了三种大肠杆菌噬菌体，并针对从不同来源获得的 96 株耐药菌株进行了评估。这些菌株的综合识别率为 43.6%，而单独识别率则从 17.0% 到 24.5% 不等。值得注意的是，在测试的噬菌体（FJ3-79、SD1-92L 和 FJ4-63）中，FJ4-63 在感染后调节宿主种群动态方面表现出独特的特性，潜伏期较短（20 分钟），迸发量较大（95.99 ± 3.61 PFU/细胞）。此外，它在 pH 值为 3-11 和低于 60°C 时表现出相对稳定性。透射电子显微镜和基因组分析表明，噬菌体 FJ4-63 属于细小病毒科达卡病毒属。其基因组由线性双链 DNA 组成，长度为 169,669 bp（包含 272 个编码序列），GC 含量为 39.76%，其中 93 个序列（34.2%）具有已知功能，其余 177 个序列被注释为假定蛋白。此外，还识别出两个 tRNA，拥有 "holin-endolysin "溶菌系统，没有检测到抗性基因或毒力基因。系统发生树和平均核苷酸同一性（ANI）分析表明，噬菌体 FJ4-63 与埃希氏菌噬菌体 C6 的相似度最高（679410.1），表明在同一分支中存在一致的密切关系。与单一噬菌体相比，由三种噬菌体组成的鸡尾酒具有更强的体外杀菌效果。在 MOI = 100 的高剂量下，它能在 1 小时内迅速完全消灭细菌，同时显著减少细菌生物膜。所有这些证据表明，溶菌噬菌体为临床治疗提供了一种有效的解决方案，噬菌体鸡尾酒在替代性治疗耐秋水仙碱大肠杆菌感染方面具有更大的潜力。

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引用次数: 0

Phage cocktail inhibits inflammation and protects the integrity of the intestinal barrier in dextran sulfate sodium-induced colitis mice model 噬菌体鸡尾酒抑制右旋糖酐硫酸钠诱导的结肠炎小鼠模型的炎症并保护肠道屏障的完整性。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-21 DOI: 10.1016/j.micpath.2024.107053

Jiazhen Xu , Ting Liu , Yingchun Shao , Qing Liu , Zongying Zhang , Yang Yuan , Shuangshuang Zhang , Yanhong Wang , Li Sun , Sha Zhou , Minglu Hao , Haoren Xiu , Xiaohui Xing , Dongming Xing

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by abdominal pain, diarrhea, and rectal bleeding. This study aims to explore the protective effects of a phage cocktail (10⁸ PFU/mL of Clostridium perfringens phage, 10⁸ PFU/mL of Escherichia coli phage, and 10⁸ PFU/mL of Salmonella phage) on a mouse colitis model induced by dextran sulfate sodium (DSS) and its potential toxic effects on normal mice. The results demonstrate that the phage cocktail significantly alleviates clinical symptoms in mice, reduces colon shortening, weight loss, and colonic pathological damage. Furthermore, the phage cocktail markedly suppresses the inflammatory response and safeguards intestinal barrier integrity in the colonic tissues of the mouse colitis model. Preliminary investigation of the toxic effects of the phage cocktail in mice indicates that continuous administration for 14 days does not yield statistically significant differences in hematological and blood biochemical parameters, and specific pathological changes are absent in histopathological examination results. The aforementioned findings suggest that the phage cocktail exhibits anti-inflammatory and intestinal barrier protective effects in the mouse colitis model, and it does not exert significant toxic side effects on mice.

溃疡性结肠炎（UC）是一种以腹痛、腹泻和直肠出血为特征的炎症性肠病。本研究旨在探讨鸡尾酒噬菌体（108 PFU/mL 产气荚膜梭菌噬菌体、108 PFU/mL 大肠杆菌噬菌体和 108 PFU/mL 沙门氏菌噬菌体）对右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎模型的保护作用及其对正常小鼠的潜在毒性作用。结果表明，鸡尾酒噬菌体能明显缓解小鼠的临床症状，减少结肠缩短、体重减轻和结肠病理损伤。此外，鸡尾酒噬菌体还能明显抑制小鼠结肠炎模型结肠组织的炎症反应，保护肠道屏障的完整性。对鸡尾酒噬菌体对小鼠毒性作用的初步研究表明，连续给药 14 天，小鼠的血液学和血液生化指标并没有显著的统计学差异，组织病理学检查结果也没有特定的病理变化。上述结果表明，鸡尾酒噬菌体在小鼠结肠炎模型中具有抗炎和保护肠道屏障的作用，对小鼠没有明显的毒副作用。

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引用次数: 0

Preparation of bovine coronavirus virus-like particles and its immunogenicity in mice and cattle 牛冠状病毒样颗粒的制备及其在小鼠和牛中的免疫原性。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-21 DOI: 10.1016/j.micpath.2024.107062

Qisheng Yu , Qing Zhu , Xiangyue Huang , Jinbo Wu , Qun Zhou , Taoyun Chen , Chenxi Zhu , Lu Ding , Gunan Deng , Yi Wang , Zhaohui Zhang , Bin Zhang

The widespread prevalence of bovine coronavirus (BCoV) disease worldwide has impacted the livestock industry economically. No effective vaccine is available in China. In this study, we produced BCoV virus-like particles (VLPs) containing E, M, N, S, and hemagglutinin-esterase (HE) proteins using a baculovirus expression system. Five recombinant baculoviruses were co-infected with Sf9 cells, and the VLPs were assembled and characterized. Mice and cattle were immunized by VLPs mixed with MF59 and CpG 55.2 adjuvants. Two doses of the VLPs/MF59/CpG vaccine were administered in mice and cattle. The immune effect of the VLPs/MF59/CpG vaccine was measured using indirect ELISA and neutralization assays. After immunization, the serum IgG-specific antibody titer against S protein and neutralization antibody titer increased to 1:1.28 × 10⁴ (p < 0.01) and 1:128 (p < 0.01) in mice, respectively. Interestingly, the high IgG antibody and neutralizing antibody titers were maintained for seven days in mice. In addition, the serum IgG-specific antibody titer against S proteins and neutralization antibody titer increased to 1:1.024 × 10⁵ and 1:512 (p < 0.05) in cattle, respectively. The high IgG antibody and neutralizing antibody titers were maintained for 21 days in cattle. Notably, BCoV VLPs group interferon-gamma (IFN-γ) lymphocytes in spleens were significantly increased (p < 0.01). These findings suggest that BCoV VLPs induced strong cellular and humoral immune responses in mice and cattle. These findings suggest that BCoV VLPs could serve as a potent immunogen for vaccine development.

牛冠状病毒（BCoV）疾病在全球广泛流行，给畜牧业带来了经济影响。中国目前尚无有效的疫苗。在这项研究中，我们利用杆状病毒表达系统生产了含有E、M、N、S和血凝素-酯酶（HE）蛋白的BCoV病毒样颗粒（VLPs）。五种重组杆状病毒共同感染了 Sf9 细胞，并组装和鉴定了 VLPs。VLP 与 MF59 和 CpG 55.2 佐剂混合后对小鼠和牛进行免疫。小鼠和牛接种了两剂 VLPs/MF59/CpG 疫苗。VLPs/MF59/CpG 疫苗的免疫效果是通过间接酶联免疫吸附试验和中和试验测定的。免疫后，血清中针对 S 蛋白的 IgG 特异性抗体滴度和中和抗体滴度分别增加到 1:1.28 × 104 （p 5）和 1:512 （p 6）。

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引用次数: 0

Influenza B virus: Target and acting mechanism of antiviral drugs 乙型流感病毒：抗病毒药物的靶点和作用机制。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-21 DOI: 10.1016/j.micpath.2024.107051

Jicheng Han, Chunhui Yang, Yan Xiao, Jingjing Li, Ningyi Jin, Yiquan Li

The influenza B virus is one of the causes of seasonal influenza, which has a long history of existence in various populations. Adolescents, children, pregnant women, the elderly, as well as patients with major diseases such as high blood pressure, diabetes, and cancer, and those with low immunity are more susceptible to infection by the influenza virus. During the influenza seasons, the influenza B virus can cause significant harm and economic burden. At present, neuraminidase inhibitors, hemagglutinin inhibitors and RNA polymerase inhibitors are the main antiviral drugs that are used in the clinical treatment of influenza B. Due to the repeated use of antiviral drugs in recent years, the emergence of resistant strains of the influenza virus exacerbated. By combining anti-viral drugs with different mechanisms of action or using a combination of traditional Chinese medicine and chemical drugs, the problem of reduced drug sensitivity can be improved. This article introduces the drug targets of the influenza B virus and the mechanism of virus resistance. It also emphasizes the clinically used antiviral drugs and their mechanisms of action, thereby providing a reference basis for the development of new anti-influenza drugs.

乙型流感病毒是季节性流感的病原体之一，长期存在于不同人群中。青少年、儿童、孕妇、老年人以及高血压、糖尿病、癌症等重大疾病患者和免疫力低下者更容易感染流感病毒。在流感季节，乙型流感病毒会造成重大危害和经济负担。由于近年来抗病毒药物的反复使用，流感病毒耐药株的出现加剧。通过联合使用不同作用机制的抗病毒药物或采用中药与化学药物相结合的方法，可以改善药物敏感性降低的问题。本文介绍了乙型流感病毒的药物靶点和病毒耐药机制。同时强调了临床上常用的抗病毒药物及其作用机制，从而为开发新的抗流感药物提供参考依据。

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引用次数: 0

Acetylation of DnaJ facilitates the proliferation of BmNPV by affecting the transport of nucleocapsids DnaJ 的乙酰化会影响核头壳的运输，从而促进 BmNPV 的增殖。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-21 DOI: 10.1016/j.micpath.2024.107050

Jiaqi Li , Siqi Xu , Chaoguang Gu , Xinyi Fan , Xizhen Zhang , Meng Miao , Wei Yu

DnaJ (Orf40), a late-expressed factor of Bombyx mori nucleopolyhedrovirus (BmNPV), is essential for the budding of virions and influences the transfer of the nucleocapsid from the nucleus to the cytoplasm. Previous studies showed that the knockdown of dnaj could prevent the nucleocapsid from exiting the nucleus, but the underlying regulatory mechanism remains unknown. In our previous acetylomic analysis of BmN cells infected with wild-type BmNPV, we found that a lysine residue (K17) was acetylated 36h post-infection, and the acetylation level of this site was upregulated about 3.5-fold. Here, we found that deacetylation of DnaJ K17 significantly inhibited viral proliferation without affecting viral DNA replication. Furthermore, deacetylation of DnaJ K17 affected the interaction with two nucleocapsid-associated proteins, Ac66 and VP80, which in turn affected the production of nucleocapsids, as well as their transport within the nucleus along F-actin fibers, leading to a decrease in the export of nucleocapsids from the nucleus. The reduced amount of nucleocapsids in the cytoplasm ultimately led to a decrease in the production of budded virions and consequently inhibited viral proliferation. In conclusion, acetylation of DnaJ affects nucleocapsid production and transport, thereby influencing viral proliferation.

DnaJ（Orf40）是一种晚期表达的蛾核多角体病毒（BmNPV）因子，对病毒的出芽至关重要，并影响核头状体从细胞核向细胞质的转移。以前的研究表明，敲除 dnaj 可以阻止核头壳离开细胞核，但其潜在的调控机制仍然未知。在之前对野生型 BmNPV 感染的 BmN 细胞进行的乙酰化分析中，我们发现感染后 36h 一个赖氨酸残基（K17）被乙酰化，且该位点的乙酰化水平上调了约 3.5 倍。在这里，我们发现 DnaJ K17 的去乙酰化能显著抑制病毒的增殖，而不影响病毒 DNA 的复制。此外，DnaJ K17的去乙酰化影响了其与两种核苷酸相关蛋白Ac66和VP80的相互作用，进而影响了核苷酸的产生及其在细胞核内沿F-肌动蛋白纤维的运输，导致核苷酸从细胞核中的输出减少。细胞质中的核苷酸数量减少最终导致出芽病毒的产生减少，从而抑制了病毒的增殖。总之，DnaJ的乙酰化会影响核苷酸的产生和运输，从而影响病毒的增殖。

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