Emerging Microbes & Infections最新文献_第6页

Isoleucine at position 137 of Hemagglutinin acts as a Mammalian adaptation marker of H9N2 Avian influenza virus. 血凝素137位异亮氨酸作为H9N2禽流感病毒的哺乳动物适应标记物。

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2025-01-16 DOI: 10.1080/22221751.2025.2455597

Weiwei Ma,Chenyang Ren,Lin Shi,Bo Meng,Yali Feng,Ying Zhang

AbstractThe H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified ten H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference. A series of reassortants between CKLN/07 and CKLN/17 were generated and their chick embryo lethality was assessed. We found that the isoleucine (I) residue at position 137 (H3 numbering) in the hemagglutinin (HA) was responsible for the chick embryo lethality of the H9N2 virus. Further studies revealed that the threonine (T) to I mutation at HA position 137 enhanced viral replication in vitro and in vivo. Moreover, the HA-T137I substitution in H9N2 avian influenza virus increased the guinea pig transmission efficiency. We also found that the HA-T137I substitution was critical for α2,6-linked sialic acid binding preference and HA activation and stability of H9N2 virus. Our findings demonstrated that HA-137I is a key molecular marker for mammalian adaptation of H9N2 AIV.

摘要H9N2亚型禽流感病毒（AIV）广泛分布于家禽和野生鸟类中，对人类也是一种威胁。在2015 - 2016年辽宁省禽流感病毒主动监测中，鉴定出10株对鸡胚具有不同致死率的H9N2毒株。选取基因组背景相似但鸡胚致死性不同的A/chicken/China/LN07/2016 （CKLN/07）和A/chicken/China/LN17/2016 （CKLN/17）两株具有代表性的菌株进行差异的分子基础分析。在CKLN/07和CKLN/17之间产生了一系列重组基因，并对其鸡胚致死性进行了评价。我们发现H9N2病毒的鸡胚致死性与血凝素（HA）第137位（H3编号）的异亮氨酸(I)残基有关。进一步的研究表明，在HA位置137的苏氨酸(T)到I的突变增强了病毒在体外和体内的复制。此外，HA-T137I在H9N2禽流感病毒中的替代作用提高了豚鼠的传播效率。我们还发现HA- t137i取代对α2,6-链唾液酸结合偏好和HA活化及H9N2病毒的稳定性至关重要。研究结果表明，HA-137I是哺乳动物适应H9N2 AIV的关键分子标记。

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引用次数: 0

Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant Serratia marcescens-induced pulmonary infection. 探讨噬菌体治疗耐多药粘质沙雷菌所致肺部感染临床应用的可行性。

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2025-01-15 DOI: 10.1080/22221751.2025.2451048

Xiangke Duan,Wenfeng Liu,Yanyu Xiao,Man Rao,Liyin Ji,Xiaofu Wan,Shuhong Han,Zixun Lin,Haichen Liu,Peifen Chen,Kun Qiao,Mingbin Zheng,Jiayin Shen,Yang Zhou,Tetsuya Asakawa,Minfeng Xiao,Hongzhou Lu

Serratia marcescens (S. marcescens) commonly induces refractory infection due to its multidrug-resistant nature. To date, there have been no reports on the application of phage treatment for S. marcescens infection. This study was conducted to explore the feasibility of phage application in treating refractory S. marcescens infection by collaborating with a 59-year-old male patient with a pulmonary infection of multidrug-resistant S. marcescens. Our experiments included three domains: i) selection of the appropriate phage, ii) verification of the efficacy and safety of the selected phage, iii) confirmation of phage-bacteria interactions. Our results showed that phage Spe5P4 is appropriate for S. marcescens infection. Treatment with phage Spe5P4 showed good efficacy, manifested as amelioration of symptoms, hydrothorax examinations, and chest computed tomography findings. Phage treatment did not worsen hepatic and renal function, immunity-related indices, or indices of routine blood examination. It did not induce or deteriorate drug resistance of the involved antibiotics. Importantly, no adverse events were reported during the treatment or follow-up periods. Thus, phage treatment showed satisfactory safety. Finally, we found that phage treatment did not increase the bacterial load, cytotoxicity, virulence, or phage resistance of S. marcescens, indicating satisfactory phage-bacteria interactions between Spe5P4 and S. marcescens, which are useful for the future application of phage Spe5P4 against S. marcescens. This work provides evidence and a working basis for further application of phage Spe5P4 in treating refractory S. marcescens infections. We also provided a methodological basis for investigating clinical application of phage treatment against multidrug-resistant bacterial infections in the future.

粘质沙雷氏菌（粘质沙雷氏菌）由于其多重耐药性质，通常会引起难治性感染。到目前为止，还没有关于噬菌体治疗粘质葡萄球菌感染的报道。本研究以一名59岁男性多药耐药粘质葡萄球菌肺部感染患者为研究对象，探讨噬菌体应用于难治性粘质葡萄球菌感染的可行性。我们的实验包括三个领域：i)选择合适的噬菌体，ii)验证所选噬菌体的有效性和安全性，iii)确认噬菌体与细菌的相互作用。结果表明，Spe5P4噬菌体适合于粘质葡萄球菌感染。Spe5P4噬菌体治疗效果良好，表现为症状改善、胸水检查及胸部ct表现。噬菌体治疗未使肝肾功能、免疫相关指标及血常规指标恶化。它不诱导或恶化所涉抗生素的耐药性。重要的是，在治疗或随访期间没有报告不良事件。因此，噬菌体治疗具有令人满意的安全性。最后，我们发现噬菌体处理并没有增加粘质葡萄球菌的细菌负荷、细胞毒性、毒力或噬菌体耐药性，表明Spe5P4与粘质葡萄球菌之间存在良好的噬菌体-细菌相互作用，这对未来应用Spe5P4噬菌体对抗粘质葡萄球菌有帮助。本研究为进一步应用噬菌体Spe5P4治疗难治性粘质葡萄球菌感染提供了依据和工作基础。为今后研究噬菌体治疗耐多药细菌感染的临床应用提供了方法学基础。

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引用次数: 0

Genotypic Variations and Clinical Implications of JEV-Associated Peripheral Nerve Injury: A Commentary on Multicenter Findings from High-Endemic Regions. jev相关周围神经损伤的基因型变异和临床意义：对高流行地区多中心研究结果的评论。

IF 8.4 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2025-01-09 DOI: 10.1080/22221751.2024.2449073

Liangping Zhang, Lei Pan, Rongqi Cao

引用次数: 0

SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signaling pathway to facilitate viral replication. SARS-CoV-2和HCoV-OC43通过激活mTORC1信号通路调节宿主m6A修饰，促进病毒复制。

IF 8.4 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2025-01-02 DOI: 10.1080/22221751.2024.2447620

Shixiong Zhou, Xianfeng Hui, Weiwei Wang, Chunbei Zhao, Meilin Jin, Yali Qin, Mingzhou Chen

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic RNA and is also present in various viral RNAs, where it plays a crucial role in regulating the viral life cycle. However, the molecular mechanisms through which viruses regulate host RNA m6A methylation are not fully understood. In this study, we reveal that SARS-CoV-2 and HCoV-OC43 infection enhance host m6A modification by activating the mTORC1 signaling pathway. Specifically, the viral non-structural protein nsp14 upregulates the expression of S-adenosylmethionine synthase MAT2A in an mTORC1-dependent manner. This mTORC1-MAT2A axis subsequently stimulates the synthesis of S-adenosylmethionine (SAM). The increase of SAM then enhances the m6A methylation of host RNA and facilitates viral replication. Our findings uncover a molecular mechanism by which viruses regulate host m6A methylation and provide insights into how SARS-CoV-2 hijacks host cellular epitranscriptomic modifications to promote its replication.

n6 -甲基腺苷（m6A）是真核生物RNA中最常见的转录后修饰，也存在于各种病毒RNA中，在调节病毒生命周期中起着至关重要的作用。然而，病毒调控宿主RNA m6A甲基化的分子机制尚不完全清楚。在这项研究中，我们发现SARS-CoV-2和HCoV-OC43感染通过激活mTORC1信号通路来增强宿主m6A修饰。具体来说，病毒非结构蛋白nsp14以mtorc1依赖的方式上调s -腺苷甲硫氨酸合成酶MAT2A的表达。mTORC1-MAT2A轴随后刺激s -腺苷甲硫氨酸（SAM）的合成。SAM的增加增强了宿主RNA的m6A甲基化，促进了病毒的复制。我们的研究结果揭示了病毒调节宿主m6A甲基化的分子机制，并为SARS-CoV-2如何劫持宿主细胞表转录组修饰以促进其复制提供了见解。

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引用次数: 0

Concurrent Severe Fever with Thrombocytopenia Syndrome Virus Outbreaks on Multiple Fox Farms, China, 2023. 2023年中国多个狐场并发发热伴血小板减少综合征病毒暴发

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2024-12-27 DOI: 10.1080/22221751.2024.2447610

Jian Sun,Lei Qian,Delong Li,Xiurong Wang,Hong Zhou,Cixiu Li,Edward C Holmes,Jianke Wang,Juan Li,Weifeng Shi

The role of farmed animals in the viral spillover from wild animals to humans is of growing importance. Between July and September of 2023 infectious disease outbreaks were reported on six Arctic fox (Vulpes lagopus) farms in Shandong and Liaoning provinces, China, which lasted for 2-3 months and resulted in tens to hundreds of fatalities per farm. Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) was identified in tissue/organ and swab samples from all the 13 foxes collected from these farms. These animals exhibited loss of appetite and weight loss, finally resulting in death. In autopsy and histopathology, prominently enlarged spleens and extensive multi-organ hemorrhage were observed, respectively, indicating severe systemic effects. Viral loads were detected in various tissues/organs, including brains from 12 of the 13 foxes. SFTSV was also detected in serum, anal swabs, as well as in environmental samples, including residual food in troughs used by dying foxes in two follow-up studies at two farms. The 13 newly sequenced SFTSV genomes shared >99.43% nucleotide identity with human strains from China. Phylogenetic analyses showed that the 13 sequences belonged to three genotypes, and that two sequences from Liaoning were genomic reassortants, indicative of multiple sources and introduction events. This study provides the first evidence of SFTSV infection, multi-tissue tropism, and pathogenicity in farmed foxes, representing an expanded virus host range. However, the widespread circulation of different genotypes of SFTSV in farmed animals from different provinces and the diverse transmission routes, highlight its increasing and noticeable public health risk in China.

在病毒从野生动物向人类扩散的过程中，养殖动物的作用越来越重要。在2023年7月至9月期间，中国山东省和辽宁省的6个北极狐（Vulpes lagopus）养殖场报告了传染病暴发，持续了2-3个月，导致每个养殖场数十至数百人死亡。在从这些农场收集的所有13只狐狸的组织/器官和拭子样本中发现了严重发热伴血小板减少综合征病毒（SFTSV）。这些动物表现出食欲不振和体重减轻，最终导致死亡。尸检和组织病理学分别观察到脾脏明显肿大和广泛的多脏器出血，提示严重的全身影响。在各种组织/器官中检测到病毒载量，包括13只狐狸中的12只的大脑。在两个农场的两项后续研究中，还在血清、肛门拭子以及环境样本中检测到SFTSV，包括在垂死狐狸使用的食槽中残留的食物。新测序的13个SFTSV基因组与中国人株核苷酸同源性为99.43%。系统发育分析表明，13条序列分属于3个基因型，其中2条来自辽宁的序列为基因组重组序列，表明其存在多来源和引进事件。本研究首次提供了SFTSV在养殖狐狸中感染、多组织趋向性和致病性的证据，代表了病毒宿主范围的扩大。然而，不同基因型的SFTSV在不同省份的养殖动物中广泛流行，传播途径多样，突显了其在中国日益增加和显著的公共卫生风险。

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引用次数: 0

Enhanced Antibody Response to the Conformational Non-RBD Region via DNA Prime-Protein Boost Elicits Broad Cross-Neutralization Against SARS-CoV-2 Variants. 通过DNA引物-蛋白增强对构象非rbd区的抗体反应引发针对SARS-CoV-2变体的广泛交叉中和

IF 8.4 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2024-12-27 DOI: 10.1080/22221751.2024.2447615

Yun-Fei Ma, Kun Chen, Bowen Xie, Jiayi Zhu, Xuan He, Chunying Chen, Yuhe Renee Yang, Ye Liu

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants. Via analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.

防止SARS-CoV-2变体的免疫逃逸对于疫苗开发至关重要，以确保对该病毒的广泛保护。RBD区域以外的构象表位是刺突蛋白的重要组成部分，但在开发具有广泛保护性的SARS-CoV-2疫苗方面受到的关注有限。在这项研究中，我们使用DNA引物蛋白增强方案来评估针对小鼠构象非rbd区的免疫应答对SARS-CoV-2病毒的广泛交叉中和潜力。针对武汉-01、Delta和Omicron亚变体，针对构象非rbd区的抗体反应增强的小鼠表现出更好的交叉中和性能。通过对构象表位分布的分析和对表位特异性结合抗体的定量分析，我们证实了针对n端结构域（NTD）超位点（一种构象非rbd表位）的结合抗体比例与SARS-CoV-2中和效价呈正相关。本研究突出了高比例构象非rbd特异性结合抗体在介导病毒交叉中和中的重要性，并为克服SARS-CoV-2变体的免疫逃逸提供了新的见解。

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引用次数: 0

To be or not to be phosphorylated: Understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56. 被磷酸化还是不被磷酸化：了解埃博拉病毒核蛋白在转录激活因子VP30和宿主磷酸酶PP2A-B56的动态相互作用中的作用

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2024-12-27 DOI: 10.1080/22221751.2024.2447612

Lennart Kämper,Ida Kuhl,Melina Vallbracht,Thomas Hoenen,Uwe Linne,Axel Weber,Petr Chlanda,Michael Kracht,Nadine Biedenkopf

Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral transcription activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in the regulation of this process by recruiting both the regulatory subunit B56 of PP2A and its substrate VP30 to initiate VP30 dephosphorylation and hence viral transcription. Both binding sites are located in close proximity to each other in NP's C-terminal disordered region. This study investigates NP's role in VP30 dephosphorylation and transcription activation, focusing on the spatial requirements of NP's binding sites. Increasing the distance between PP2A-B56 and VP30 at the NP interface revealed that close spatial and orientational contact is necessary for efficient VP30 dephosphorylation and viral transcription. Longer distances were lethal for recombinant EBOV except when a compensatory mutation, NP-T603I, occurred. This mutation, located between the NP binding sites for PP2A-B56 and VP30, fully restored functionality. Mass spectrometry showed that T603 is phosphorylated in recEBOV-NPwt virions. Mutational analysis indicated that T603I facilitates VP30 dephosphorylation in otherwise lethal recEBOV and that dynamic phosphorylation of NP-T603 is important for efficient primary viral transcription in the WT context. These findings emphasize the critical and evolutionarily pressured interplay between VP30 and PP2A-B56 within the NP C-terminal disordered region and highlight the important role of NP on the regulation of viral transcription during the EBOV life cycle.

埃博拉病毒（EBOV）的转录基本上是通过宿主磷酸酶PP2A对其病毒转录激活子VP30的动态去磷酸化来调节的。核蛋白NP通过招募PP2A的调控亚基B56及其底物VP30来启动VP30的去磷酸化和病毒转录，从而成为这一过程的第三个关键参与者。这两个结合位点位于NP的c端无序区，彼此距离很近。本研究探讨了NP在VP30去磷酸化和转录激活中的作用，重点研究了NP结合位点的空间要求。增加PP2A-B56和VP30在NP界面上的距离表明，密切的空间和方向接触是VP30高效去磷酸化和病毒转录所必需的。除了发生代偿性突变NP-T603I外，较长距离的传播对重组EBOV是致命的。该突变位于PP2A-B56和VP30的NP结合位点之间，完全恢复了功能。质谱分析显示，T603在recEBOV-NPwt病毒粒子中被磷酸化。突变分析表明，T603I在致命的recEBOV中促进VP30的去磷酸化，而NP-T603的动态磷酸化对于WT环境下高效的初级病毒转录很重要。这些发现强调了NP c端紊乱区VP30和PP2A-B56之间的关键和进化压力相互作用，并强调了NP在EBOV生命周期中对病毒转录调控的重要作用。

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引用次数: 0

The Prevalence of Low-level Viraemia and Its Association with Virological Failure in People Living With HIV: A Systematic Review and Meta-Analysis. HIV感染者低水平病毒血症的流行及其与病毒学失败的关系：一项系统综述和荟萃分析。

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2024-12-27 DOI: 10.1080/22221751.2024.2447613

Shengnan Zhao,Wenjing Wang,Sibo Li,Jiaze He,Wenshan Duan,Zhen Fang,Xiaoran Ma,Zhen Li,Caiping Guo,Wen Wang,Hao Wu,Tong Zhang,Xiaojie Huang

Low-level viraemia (LLV) following antiretroviral therapy (ART) in people living with HIV (PLWH) has not received sufficient attention. To the determine the prevalence of LLV and its association with virological failure (VF), we systematically reviewed evidence-based interventions for PLWH. We searched PubMed, the Cochrane Library, Embase, and Web of Science from inception to 22 May 2024. Cohorts with samples sizes smaller than 1000 in size were excluded. Data from 16 cohort studies, encompassing 1,349,306 PLWH, revealed a pooled prevalence of LLV of 13.81%. Relative risk (RR) and 95% confidence intervals (CI) identified the following risk factors for LLV: viral load (VL) ≥ 105 copies/mL at baseline (1.79, 1.11-2.88), AIDS-defined illness at baseline (1.24, 1.10-1.40), and protease inhibitor-based regimen at ART initiation (1.53, 1.45-1.62) are the risk factors for LLV. Conversely, CD4 count ≥200 cells/μL at baseline (0.90, 0.82-0.98), non-nucleoside reverse transcriptase inhibitor-based regimen (0.81, 0.68-0.96) and the integrase strand transfer inhibitor (INSTI)-based regimen (0.60, 0.42-0.85) were associated with a reduced risk of LLV. Pooling the adjusted hazard ratio (aHR) and the 95% CI, we found that LLV increased the risk of VF with rising VL among 96,711 PLWH (aHR 2.77, 95% CI 2.03-3.76) and increased the risk of all-cause mortality at high VL levels among 14,229 PLWH (aHR 1.66, 95% CI 1.16-2.37). Therefore, the prevalence of LLV in PLWH should not be overlooked. This study aims to guide better management strategies to improve clinical outcomes in patients with LLV.

艾滋病毒感染者（PLWH）抗逆转录病毒治疗（ART）后的低水平病毒血症（LLV）尚未得到足够的重视。为了确定LLV的患病率及其与病毒学失败（VF）的关系，我们系统地回顾了PLWH的循证干预措施。我们检索了PubMed、Cochrane图书馆、Embase和Web of Science从成立到2024年5月22日。样本量小于1000的队列被排除。来自16项队列研究的数据，包括1,349,306名PLWH，显示LLV的总患病率为13.81%。相对危险度（RR）和95%置信区间（CI）确定了LLV的以下危险因素：基线时病毒载量(VL)≥105拷贝/mL(1.79, 1.11-2.88)，基线时艾滋病定义的疾病（1.24,1.10-1.40），以及开始ART时基于蛋白酶抑制剂的方案（1.53,1.45-1.62）是LLV的危险因素。相反，CD4计数≥200细胞/μL基线（0.90,0.82-0.98），非核苷逆转录酶抑制剂方案（0.81,0.68-0.96）和整合酶链转移抑制剂（INSTI）方案（0.60,0.42-0.85）与LLV风险降低相关。综合校正后的风险比（aHR）和95% CI，我们发现在96711名PLWH中，LLV增加了VF的风险，随着VL的升高（aHR 2.77, 95% CI 2.03-3.76），并增加了14229名PLWH中高VL水平的全因死亡风险（aHR 1.66, 95% CI 1.16-2.37）。因此，不应忽视PLWH中LLV的患病率。本研究旨在指导更好的管理策略，以改善LLV患者的临床预后。

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引用次数: 0

Genomic epidemiology and evolution of Bordetella pertussis under the vaccination pressure of acellular vaccines in Beijing, China, 2020-2023. 2020-2023年中国北京地区无细胞疫苗接种压力下百日咳博德泰拉基因组流行病学及进化

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2024-12-26 DOI: 10.1080/22221751.2024.2447611

Zhen Li,Fei Xiao,Yue Hou,Bin Jia,Ji Zhuang,Yang Cao,Jianxin Ma,Jianhong Zhao,Zengquan Xu,Zhe Jia,Fang Liu,Lin Pang,Jie Liu

Pertussis (or whooping cough) has experienced a global resurgence despite widespread vaccine efforts. In China, the incidence of pertussis has rapidly increased, particularly following the COVID-19 pandemic. Whole-genome sequencing analysis was performed on 60 Bordetella pertussis strains isolated in Beijing from 2020 to 2023, and the sequences were compared with those of 635 strains from China and 943 strains from other countries. In this study, the genetic evolution of B. pertussis was investigated, focusing on key virulence genes (ptxP, ptxA, prn, fim2, fim3, tcfA) and the resistance-related locus A2047 across different periods and regions. The dominant antigen genotype among the 60 isolates was ptxP3/prn2/ptxA1/fim2-1/fim3-1/tcfA2 (88.3%), differing from the prevalent genotype ptxP-1/prn-1/ptxA-1 in Beijing prior to 2019 and the vaccine strain genotype ptxP-1/prn-1/ptxA-2/fim2-1/fim3-1/tcfA2. Evolutionary analysis revealed significant genetic shifts associated with the introduction of vaccines, particularly acellular vaccines. Initially, the prevalent genotypes included ptxP-1, prn-1, ptxA-2, fim2-2, and fim3-2. However, currently, ptxP-3, prn-2 and ptxA-1 have become predominant globally, indicating vaccine-induced selection pressure. Additionally, all 60 isolated strains (100%) presented the A2047G mutation associated with erythromycin resistance, of which ptxP3 accounted for 91.7%. Macrolide-resistant Bordetella pertussis (MRBP) is widespread in China, and the prevalence of ptxP3-MRBP may be increasing. The significant changes of dominance of subtypes in Beijing in recent years underscore the need for continuous surveillance and adaptation of pertussis vaccination strategies.

尽管广泛接种疫苗，百日咳（或百日咳）仍在全球卷土重来。在中国，百日咳的发病率迅速增加，特别是在COVID-19大流行之后。对2020 - 2023年北京地区分离的60株百日咳博德tella百日咳菌株进行全基因组测序分析，并与国内635株和国外943株进行比较。本研究通过对百日咳关键毒力基因（ptxP、ptxA、prn、fim2、fim3、tcfA）和抗性相关位点A2047在不同时期和不同地区的遗传进化进行研究。60株分离株的优势抗原基因型为ptxP3/prn2/ptxA1/ fim1 -1/fim3-1/tcfA2(88.3%)，与2019年之前北京流行的基因型ptxP-1/prn-1/ptxA-1和疫苗株基因型ptxP-1/prn-1/ptxA-2/fim2-1/fim3-1/tcfA2不同。进化分析揭示了与疫苗，特别是非细胞疫苗的引入相关的重大遗传变化。最初，流行的基因型包括ptxP-1、prn-1、ptxA-2、fim2-2和fim3-2。然而，目前ptxP-3、prn-2和ptxA-1已在全球占据主导地位，这表明疫苗诱导的选择压力。60株分离菌株（100%）均存在与红霉素耐药相关的A2047G突变，其中ptxP3突变占91.7%。耐大环内酯类药物百日咳（MRBP）在中国广泛存在，ptxP3-MRBP的流行可能呈上升趋势。近年来北京地区百日咳亚型优势度的显著变化强调了持续监测和适应百日咳疫苗接种策略的必要性。

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引用次数: 0

Precursor of H-Type II Histo-Blood Group Antigen and Subterminal Sialic Acids on Gangliosides Are Significantly Implicated in Cell Entry and Infection by a Porcine P[11] Rotavirus. h型组织血型抗原前体和神经节苷上的亚末端唾液酸与猪P[11]轮状病毒的细胞侵入和感染有重要关系

IF 13.2 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections

Pub Date : 2024-12-26 DOI: 10.1080/22221751.2024.2447608

Miaomiao Yan,Ang Su,Denise Meyer,Gleyder Roman Sosa,Henrik Fritsch,Malte Pitters,Nicole Fischer,Georg Herrler,Paul Becher

Rotaviruses, non-enveloped viruses with a double-stranded RNA genome, are the leading etiological pathogen of acute gastroenteritis in young children and animals. The P[11] genotype of rotaviruses exhibits a tropism for neonates. In the present study, a binding assay using synthetic oligosaccharides demonstrated that the VP8* protein of P[11] porcine rotavirus (PRV) strain 4555 binds to lacto-N-neotetraose (LNnT) with the sequence Galβ1,4-GlcNAcβ1,3-Galβ1,4-Glc, one of the core parts of histo-blood group antigen (HBGA) and milk glycans. However, infections were significantly inhibited by blocking of endogenous monosialoganglioside (GM) GM1a with cholera toxin B subunit and preincubation of the virus with exogenous GM1a, suggesting that GM1a is involved in the infection of P[11] PRV 4555. In addition to GM1a, preincubation of the virus with exogenous disialogangliosides (GD) GD1a, GD1b, and trisialoganglioside (GT) GT1b also prevented infection. In contrast, exogenous ganglioside GM3 only inhibited infections at an early time point, and exogenous asyalosphingolipids GA1 and LacCer did not show any inhibitory effect on infections. This indicates that P[11] PRV 4555 preferentially utilizes gangliosides containing subterminal sialic acids. Further experiments revealed that P[11] PRV 4555 infections were prevented by preincubation of the virus with Neu5Ac and Neu5Gc. These results confirmed that sialic acids are essential for P[11] PRV 4555 cell entry, despite the classification as NA-resistant strain. Overall, our results proved that P[11] rotavirus not only binds to the Gal-GlcNAc motif but also utilizes gangliosides containing subterminal sialic acids.

轮状病毒是具有双链RNA基因组的非包膜病毒，是幼儿和动物急性胃肠炎的主要病原学病原体。轮状病毒的p[11]基因型在新生儿中表现出趋向性。本研究利用合成寡糖结合实验证实，猪轮状病毒（PRV） 4555株的VP8*蛋白与组织-血群抗原（HBGA）核心部分之一的乳糖-n -新四糖（LNnT）结合，其序列为galβ 1,4- glcnac β1,3- galβ 1,4- glc。然而，通过用霍乱毒素B亚基阻断内源性单唾液神经节苷（GM） GM1a和用外源性GM1a预孵育病毒，可以显著抑制感染，这表明GM1a参与了P[11] PRV 4555的感染。除GM1a外，将病毒与外源性双胞脂苷（GD） GD1a、GD1b和三胞脂苷（GT） GT1b预孵育也可预防感染。相比之下，外源性神经节苷脂GM3仅在早期时间点抑制感染，外源性无突触鞘脂GA1和LacCer对感染没有任何抑制作用。这表明p[11] PRV 4555优先利用含有亚末端唾液酸的神经节苷脂。进一步的实验表明，通过与Neu5Ac和Neu5Gc预孵育，p[11] PRV 4555感染可被阻止。这些结果证实，尽管p[11] PRV 4555被归类为na抗性菌株，但唾液酸对其进入细胞是必需的。总之，我们的研究结果证明p[11]轮状病毒不仅结合Gal-GlcNAc基序，而且利用含有亚末端唾液酸的神经节苷脂。

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