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COVID-19 mRNA vaccine immune response to the addition of osteopathic manipulative treatment with lymphatic pumps: a randomized controlled trial COVID-19 mRNA疫苗对添加淋巴泵整骨疗法的免疫应答:一项随机对照试验
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-07-14 DOI: 10.1016/j.virusres.2025.199607
Eric S. Martinez , Sebastien Fuchs , Hendrik Szurmant , Xunxuan Chen , Andrew Comer , Edward Lee , Raymond Hruby , Rebecca Giusti , Brian Loveless , Julieanne P. Sees , Paula Crone , Laura J. Peek , Gary Pestano , Bin Xie , Joseph Zammuto , Sir Robert Hostoffer Jr. , Jesus Sanchez Jr.
Osteopathic manipulative treatment (OMT) has demonstrated immune augmentation in preclinical studies, but direct evidence in humans is lacking. We conducted a randomized controlled trial on the addition of OMT in subjects receiving their first Pfizer-BioNTech (BNT162b2) COVID-19 vaccination in 2021. Subjects were randomized to either receive OMT at each vaccination or not. We measured anti-spike protein, anti-nucleocapsid, and neutralizing antibodies. Primary endpoints were time-resolved and cumulative anti-SARS-CoV-2 spike protein antibody titers. Secondary endpoints were breakthrough infection symptom frequency, severity, and duration. 104 subjects were randomly assigned to control or OMT group, with 91 subjects completing the primary vaccination series. Initial antibody titers separated subjects into 51 COVID-19-naïve and 40 COVID-19-pre-exposed. COVID19-naïve subjects were selected for analysis based on data homogeneity. In this cohort, the OMT group showed significantly increased anti-SARS-CoV-2 spike protein antibody titers at 3 weeks vs controls (p = 0.038). Cumulative titers in this cohort, were significantly increased in the OMT group at 5 weeks (p = 0.046) and at 13 weeks (p = 0.009) compared to controls. An intention-to-treat (ITT) analysis of all subjects revealed significant differences in titers between the OMT group and controls at 3 weeks (p < 0.001) and at 13 weeks for AUC titers (p = 0.035) as compared to controls. The COVID-19- pre-exposed group showed no significant differences. Both groups had 10 breakthrough infections, but the OMT group experienced fewer and less severe symptoms, with symptom duration reduced from 8 days in controls to 4.5 days in the OMT group (p = 0.013). Medication duration was shorter in the OMT group, 1.5 days vs 5 days (p = 0.014). OMT-treated subjects developed quicker and stronger vaccine-induced antibody titers and had significantly shorter and less severe breakthrough symptoms, suggesting OMT may enhance immune responses to COVID19 vaccination.
骨科手法治疗(OMT)在临床前研究中已经证明了免疫增强,但在人体中缺乏直接证据。我们在2021年首次接种辉瑞- biontech (BNT162b2) COVID-19疫苗的受试者中进行了一项添加OMT的随机对照试验。受试者在每次接种疫苗时随机接受或不接受OMT。我们检测了抗刺突蛋白、抗核衣壳和中和抗体。主要终点为时间分辨和累积抗sars - cov -2刺突蛋白抗体滴度。次要终点是突破感染症状的频率、严重程度和持续时间。104名受试者被随机分配到对照组或OMT组,其中91名受试者完成了一次疫苗接种系列。初始抗体滴度将受试者分为51名COVID-19-naïve和40名covid -19预暴露者。根据数据同质性选取COVID19-naïve受试者进行分析。在该队列中,与对照组相比,OMT组在3周时抗sars - cov -2刺突蛋白抗体滴度显著增加(p=0.038)。在该队列中,与对照组相比,OMT组在5周(p=0.046)和13周(p=0.009)时的累积滴度显著增加。对所有受试者的意向治疗(ITT)分析显示,在3周时,OMT组和对照组的滴度有显著差异(p
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引用次数: 0
Corrigendum to “Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells” [Virus Research 192 (2014) 34-45] “传染性胃肠炎病毒和猪流行性腹泻病毒感染诱导极化IPEC-J2细胞紧密连接和微丝的剧烈变化”[病毒研究192(2014)34-45]。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-07-09 DOI: 10.1016/j.virusres.2025.199603
Shanshan Zhao, Junkai Gao, Liqi Zhu, Qian Yang
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引用次数: 0
Mosquito-borne alphaviruses in Zambia: Isolation and characterization of Eilat and Sindbis viruses 赞比亚蚊媒甲病毒:埃拉特和辛德比斯病毒的分离和鉴定
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-07-07 DOI: 10.1016/j.virusres.2025.199604
Chadwic De’Sean Mears , Koshiro Tabata , Takuma Ariizumi , Bernard M. Hang'ombe , Yongjin Qiu , Hayato Harima , Masahiro Kajihara , William W. Hall , Michihito Sasaki , Hirofumi Sawa , Yasuko Orba
Alphaviruses in the family Togaviridae include zoonotic arthropod-borne viruses, including Sindbis virus (SINV), chikungunya virus, as well as insect-specific viruses such as Eilat virus (EILV). Previous investigations of alphaviruses in Zambia have identified a novel insect-specific alphavirus, Mwinilunga alphavirus in mosquitoes. Further ongoing surveillance resulted in the isolation of EILV and SINV for the first time in Zambia. Here, these alphaviruses were characterized in terms of growth kinetics in cells, and molecular phylogenetic relatedness to other alphaviruses. Zambian EILV (strain zmq19_M44) exhibited a close phylogenetic relationship with other insect-specific alphaviruses and shared a close nucleotide identity to those of EILV isolate (90.4 %) and Mwinilunga alphavirus (75.5 %). EILV zmq19_M44 attained a saturating titer in C6/36 cells at 6–8-days post infection but was unable to replicate in mammalian cells. Phylogenetic analysis revealed the Zambian SINV (strain zmq17_M115) belongs in Clade D of SINV Genotype 1 along with the Kenyan isolate BONI 584 from Central Africa. The growth of the SINV zmq17_M115 was comparable to that of the prototype SINV strain AR339 in mammalian cells but was statistically different in insect cells. Our findings will contribute to public health measures for the control of alphaviral diseases in Zambia.
托加病毒科的甲病毒包括人畜共患节肢动物传播的病毒,包括辛德比斯病毒(SINV)、基孔肯雅病毒以及埃拉特病毒(EILV)等昆虫特异性病毒。先前在赞比亚对甲病毒进行的调查已在蚊子中发现了一种新的昆虫特异性甲病毒Mwinilunga甲病毒。进一步的持续监测导致赞比亚首次分离出艾滋病毒和新冠病毒。在这里,这些甲病毒在细胞中的生长动力学以及与其他甲病毒的分子系统发育相关性方面被表征。赞比亚病毒株zmq19_M44与其他昆虫特异性甲病毒有密切的系统发育关系,与病毒株(90.4%)和Mwinilunga甲病毒(75.5%)核苷酸同源。感染后6 - 8天,EILV zmq19_M44在C6/36细胞中达到饱和滴度,但无法在哺乳动物细胞中复制。系统发育分析表明,赞比亚的SINV(菌株zmq17_M115)与肯尼亚的BONI 584一起属于SINV基因1型的D支系。SINV zmq17_M115在哺乳动物细胞中的生长与原型SINV菌株AR339相当,但在昆虫细胞中的生长差异有统计学意义。我们的发现将有助于赞比亚控制甲型病毒性疾病的公共卫生措施。
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引用次数: 0
A 15-year study of neuraminidase mutations and the increasing of S247N mutation in Spain 西班牙神经氨酸酶突变和S247N突变增加的15年研究
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-26 DOI: 10.1016/j.virusres.2025.199599
Iván Sanz-Muñoz , Alejandro Martín-Toribio , Adrián García-Concejo , Irene Arroyo-Hernantes , Marina Toquero-Asensio , Javier Sánchez-Martínez , Carla Rodríguez-Crespo , Silvia Rojo-Rello , Marta Domínguez-Gil , Eduardo Tamayo-Gómez , Marta Hernández-Pérez , José M Eiros
The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations, especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain. To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences, and analyzed the resistance mutations using FluSurver software. Our results showed that the occurrence of NA resistance mutations remained constant in the four viruses during the 15 seasons evaluated, being around 0.5–5 %. Most of the resistance was found in the A(H1N1)pdm09 subtype (around 70 %), especially from the 2023–2024 season onwards, when a significant increase in the occurrence of S247N mutation was observed. The occurrence of this type of mutation before 2022 was rare, but in the 2023–2024 season a total of 44 influenza viruses harboring S247N mutations were detected, while in the other years, only two cases were observed. Some studies have described a significant increase in this mutation over the past two seasons and although it appears to confer only slightly reduced inhibition to oseltamivir, its increase is noteworthy and should be a reason for increased their vigilance.
针对流感的治疗武器库极其有限,并且由于突变的出现,特别是在神经氨酸酶(NA)基因中,经常出现耐药性。本研究旨在评估15年来西班牙NA突变的演变。为此,我们利用GISAID数据库下载了共11125个甲型H1N1流感病毒pdm09、a (H3N2)、B/Victoria和B/Yamagata NA病毒序列,并使用FluSurver软件分析了抗性突变。结果表明,在15个季节中,4种病毒的NA抗性突变发生率保持不变,约为0.5-5%。大多数耐药发生在甲型H1N1 pdm09亚型(约70%),特别是从2023-2024年季节开始,观察到S247N突变的发生显著增加。在2022年之前,这种类型的突变很少发生,但在2023-2024年流感季节,共检测到44例携带S247N突变的流感病毒,而在其他年份,仅观察到2例。一些研究描述了在过去两个季节中这种突变的显著增加,尽管它似乎只使奥司他韦的抑制作用略有降低,但它的增加是值得注意的,应该是提高警惕的一个原因。
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引用次数: 0
A systematic review of T cell epitopes defined from the proteome of human immunodeficiency virus 从人类免疫缺陷病毒蛋白质组中确定的T细胞表位的系统综述
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-23 DOI: 10.1016/j.virusres.2025.199602
Yan Ding , Ling Huang , Yandan Wu , Jialai Yan

Background

Human immunodeficiency virus (HIV) persists as a formidable and far - reaching threat without a cure. T cells are crucial for antiviral immunity and pathology in HIV patients, with specific T cell epitopes potentially key to effective therapies and HIV cure methods.

Methods

Identifying sufficient T-cell epitopes within the HIV proteome holds great significance. It can not only substantially accelerate the development of T-cell epitope-based vaccines but also enable a highly precise evaluation of the host's HIV-specific cellular immunity. This research provides an overview of functionally verified T-cell epitopes derived from HIV antigens, the human leukocyte antigen (HLA) alleles, as well as the screening and identification strategies.

Results

Totally, 239 and 82 epitopes have been verified for CD8+ T-cell and CD4+ T-cell respectively by functional experiments. The majority are presented by various HLA supertypes, such as HLA-B35, B5301, A6802 or A0201, and DRB1 molecules. Furthermore, 74 % of the epitopes for CD8+T-cell belong to Gag, Pol, as well as Nef Protein while 68 % of the CD4+ T-cell epitopes originate from Gag protein. Antigenic peptides of HIV-1 subtypes A/B/C/D/CRF01_AE account for 11.43 %, 58.26 %, 21.69 %, 4.96 %, and 3.65 %, respectively.

Conclusions

The 321 T-cell epitope repertoires of HIV encompass the HLA polymorphisms of the main populations and subtypes in a particular geographical area. These epitope catalogs provide strong support for researching therapeutic vaccines, specific T-cell detection, and the interaction mechanism between HIV and the immune system. However, the limitations of the identified T-cell epitope library, the polymorphism of HLA molecules, and the high mutation rate of HIV require more research to cover the entire HIV proteome and the comprehensive landscape of T-cell epitopes in global patients.
人类免疫缺陷病毒(HIV)一直是一种无法治愈的可怕而深远的威胁。T细胞对HIV患者的抗病毒免疫和病理至关重要,特定的T细胞表位可能是有效治疗和HIV治愈方法的关键。方法在HIV蛋白组中发现足够的t细胞表位具有重要意义。它不仅可以大大加速基于t细胞表位的疫苗的开发,而且可以高度精确地评估宿主的hiv特异性细胞免疫。本研究概述了功能性验证的源自HIV抗原的t细胞表位,人类白细胞抗原(HLA)等位基因,以及筛选和鉴定策略。结果CD8+ t细胞和CD4+ t细胞经功能实验分别鉴定出239个和82个表位。大多数是各种HLA超型,如HLA- b35、B5301、A6802或A0201和DRB1分子。此外,CD8+ t细胞74%的表位属于Gag、Pol和Nef蛋白,而CD4+ t细胞68%的表位来自Gag蛋白。HIV-1 A/B/C/D/CRF01_AE亚型抗原肽分别占11.43%、58.26%、21.69%、4.96%和3.65%。结论321个HIV t细胞表位库包含了特定地理区域主要人群和亚型的HLA多态性。这些表位目录为研究治疗性疫苗、特异性t细胞检测以及HIV与免疫系统的相互作用机制提供了强有力的支持。然而,由于已鉴定的t细胞表位文库的局限性、HLA分子的多态性以及HIV的高突变率,需要更多的研究来覆盖整个HIV蛋白质组和全球患者t细胞表位的综合景观。
{"title":"A systematic review of T cell epitopes defined from the proteome of human immunodeficiency virus","authors":"Yan Ding ,&nbsp;Ling Huang ,&nbsp;Yandan Wu ,&nbsp;Jialai Yan","doi":"10.1016/j.virusres.2025.199602","DOIUrl":"10.1016/j.virusres.2025.199602","url":null,"abstract":"<div><h3>Background</h3><div>Human immunodeficiency virus (HIV) persists as a formidable and far - reaching threat without a cure. T cells are crucial for antiviral immunity and pathology in HIV patients, with specific T cell epitopes potentially key to effective therapies and HIV cure methods.</div></div><div><h3>Methods</h3><div>Identifying sufficient T-cell epitopes within the HIV proteome holds great significance. It can not only substantially accelerate the development of T-cell epitope-based vaccines but also enable a highly precise evaluation of the host's HIV-specific cellular immunity. This research provides an overview of functionally verified T-cell epitopes derived from HIV antigens, the human leukocyte antigen (HLA) alleles, as well as the screening and identification strategies.</div></div><div><h3>Results</h3><div>Totally, 239 and 82 epitopes have been verified for CD8<sup>+</sup> T-cell and CD4<sup>+</sup> T-cell respectively by functional experiments. The majority are presented by various HLA supertypes, such as HLA-B35, B5301, A6802 or A0201, and DRB1 molecules. Furthermore, 74 % of the epitopes for CD8<sup>+</sup>T-cell belong to Gag, Pol, as well as Nef Protein while 68 % of the CD4<sup>+</sup> T-cell epitopes originate from Gag protein. Antigenic peptides of HIV-1 subtypes A/B/C/D/CRF01_AE account for 11.43 %, 58.26 %, 21.69 %, 4.96 %, and 3.65 %, respectively.</div></div><div><h3>Conclusions</h3><div>The 321 T-cell epitope repertoires of HIV encompass the HLA polymorphisms of the main populations and subtypes in a particular geographical area. These epitope catalogs provide strong support for researching therapeutic vaccines, specific T-cell detection, and the interaction mechanism between HIV and the immune system. However, the limitations of the identified T-cell epitope library, the polymorphism of HLA molecules, and the high mutation rate of HIV require more research to cover the entire HIV proteome and the comprehensive landscape of T-cell epitopes in global patients.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199602"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Accelerating vaccine development: Plug-and-play platforms for emerging infectious diseases 加速疫苗开发:新发传染病的即插即用平台。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-21 DOI: 10.1016/j.virusres.2025.199601
Kairui Yang
Emerging pathogens underscore an urgent need for rapidly developed vaccines to minimize mortality and societal disruption. Traditional vaccine development requires time spans of years, making it ill-suited to fast evolving viruses that can overwhelm healthcare systems and economies. In response, plug-and-play vaccine platforms offer a more agile solution. By reusing proven backbones, they reduce the repetitive safety and production steps otherwise required for each new pathogen, thus accelerating both regulatory approval and large-scale manufacturing. In parallel, artificial intelligence and computational tools enable faster antigen and epitope identification, more accurate immune response modeling, and improved vaccine design. These innovations have already shortened timelines and enhanced efficacy.
新出现的病原体强调迫切需要迅速开发疫苗,以尽量减少死亡率和社会混乱。传统的疫苗开发需要数年的时间跨度,这使得它不适合快速进化的病毒,这些病毒可能会使卫生保健系统和经济不堪重负。为此,即插即用疫苗平台提供了更灵活的解决方案。通过重复使用经过验证的骨干,它们减少了每一种新病原体所需的重复安全和生产步骤,从而加快了监管审批和大规模生产。与此同时,人工智能和计算工具能够更快地识别抗原和表位,更准确地建立免疫反应模型,并改进疫苗设计。这些创新已经缩短了时间,提高了效率。
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引用次数: 0
Evolutionary characterization and pathogenicity of a porcine G9P[23] rotavirus with gene segments linked to canine and giant panda strains 猪G9P[23]轮状病毒与犬和大熊猫毒株相关基因片段的进化特征和致病性
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-15 DOI: 10.1016/j.virusres.2025.199600
Xi Li , Jingjing Wang , Yuankui Zhang , Yarong Zhao , Wenjun Liu , Yanli Shi
Porcine rotavirus A (RVA) has emerged as an increasingly consequential zoonotic pathogen, causing severe intestinal disorders across diverse mammalian species, including humans. During of an outbreak that struck nursing piglets with diarrhea, a porcine G9P[23] rotavirus, named as RVA/Pig-wt/China/ZJ03/2022/G9P[23] (hereafter referred to as ZJ03), was identified. To further elucidate the evolutionary diversity of ZJ03, a comprehensive analysis of all genome segments was conducted. The genome constellation was identified as G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Nucleotide sequence identity and phylogenetic analyses indicated that the VP3 and NSP1 genes of ZJ03 are most closely related to the corresponding genes of the giant panda strain and the dog strain, respectively, showing the highest homology at 95.73 % identity and 94.64 %. The remaining genes demonstrated the most intimate relationship with porcine strains. Their highest homology levels ranged from 95.98 % to 99.49 % similarity. Therefore, evidence suggests interspecies transmission and genetic reassortment events between porcine, canine, and giant panda rotavirus strains. To evaluate the pathogenicity of ZJ03 strain, we experimentally infected 3-day-old piglets oral inoculation with the PoRV ZJ03 strain at a dose of 2 × 10^5.5 TCID50/ml per piglet. The infection resulted in severe diarrhea in all piglets, which occurred at 48 h post-infection (hpi), accompanied by sustained viral shedding and characteristic small intestinal villous atrophy, indicating significant damage to the intestinal epithelium. In vitro, ZJ03 exhibited efficient replication kinetics in MA104 cells, reaching peak titers of 10^9.25 TCID50/mL at 36 h post-infection. This study reports the first documented case of a novel porcine G9P[23] rotavirus with gene segments linked to canine and giant panda strains in mainland China, characterized by high viral titer and virulence. The findings highlight the emergence of a previously unrecorded RVA strain with significant virological and ecological implications.
猪轮状病毒A (RVA)已成为一种越来越重要的人畜共患病原体,在包括人类在内的多种哺乳动物物种中引起严重的肠道疾病。在一次以腹泻感染哺乳仔猪的疫情中,发现了一种猪G9P[23]轮状病毒,命名为RVA/Pig-wt/China/ZJ03/2022/G9P[23](以下简称ZJ03)。为了进一步阐明ZJ03的进化多样性,我们对其所有基因组片段进行了综合分析。基因组群鉴定为G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1。核苷酸序列鉴定和系统发育分析表明,ZJ03的VP3和NSP1基因分别与大熊猫品系和犬品系的对应基因亲缘关系最为密切,同源性最高,分别为95.73%和94.64%。其余基因与猪株的关系最为密切。最高同源度为95.98% ~ 99.49%。因此,有证据表明猪、犬和大熊猫轮状病毒毒株之间存在种间传播和基因重组事件。为了评估ZJ03菌株的致病性,我们实验用2 × 10^5.5 TCID50/ml /头仔猪口服接种ZJ03菌株感染3日龄仔猪。所有仔猪在感染后48小时出现严重腹泻,并伴有持续的病毒脱落和特征性的小肠绒毛萎缩,表明肠上皮受到严重损伤。在体外,ZJ03在MA104细胞中表现出高效的复制动力学,在感染后36小时达到峰值滴度10^9.25 TCID50/mL。本研究报告了中国大陆首次记录的新型猪G9P[23]轮状病毒,其基因片段与犬和大熊猫毒株相关,具有高病毒滴度和毒力的特点。这些发现强调了一种以前未记录的RVA菌株的出现,具有重要的病毒学和生态学意义。
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引用次数: 0
Characterization of antigenically dominant regions in the hemagglutinin protein of B/victoria-lineage influenza B virus using monoclonal antibody escape mutants 利用单克隆抗体逃逸突变体研究B/维多利亚乙型流感病毒血凝素蛋白抗原优势区
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-14 DOI: 10.1016/j.virusres.2025.199598
Yoko Matsuzaki , Kanetsu Sugawara , Yoko Kadowaki , Yuko Kidoguchi , Yoshitaka Shimotai , Katsumi Mizuta
As of 2024, B/Victoria-lineage strains have emerged as the predominant influenza B viruses globally. To elucidate the antigenic regions responsible for variation within this lineage, three monoclonal antibodies (MAbs) targeting the hemagglutinin (HA) protein were employed to generate escape mutants of the B/Victoria strain B/Aichi/20/99, which was isolated approximately 10 years after the B/Victoria and B/Yamagata lineages began cocirculating. A total of 45 escape mutants were obtained. Sequencing of their HA genes identified six amino acid substitutions at four sites within two key antigenic regions—the 160-loop and 190-helix—specifically, N165Y, N165S, K167R, and an asparagine insertion between residues 164 and 165 in the 160-loop; and K203R and K203N in the 190-helix (numbering is based on the B/Brisbane/60/2008 HA sequence). Hemagglutination inhibition (HI) assays revealed that two MAbs affected binding of both mutants with mutations in the 160-loop and those with a mutation at residue 203. Mutations in the 160-loop did not affect reactivity with antiserum against the parental B/Aichi/20/99 strain, whereas K203N substitution reduced antiserum reactivity, indicating the antigenic importance of this residue. Further HI analyses using eight B/Victoria lineage strains isolated between 1997 and 2021 showed that all three MAbs lost reactivity with strains isolated after 2016, while the antiserum demonstrated reduced reactivity. Notably, the current vaccine strain, B/Austria/1359417/2021, which harbors substitutions at positions 150 and 203, also exhibited diminished reactivity. These findings suggest that both the 150-loop and 190-helix constitute antigenically dominant sites that contribute to immune escape and the emergence of drift variants within the B/Victoria-lineage.
截至2024年,B/维多利亚谱系毒株已成为全球主要的乙型流感病毒。为了阐明该谱系变异的抗原区域,利用3种靶向血凝素(HA)蛋白的单克隆抗体(mab)产生B/Victoria菌株B/Aichi/20/99的逃逸突变体,该突变体是在B/Victoria和B/Yamagata谱系开始共循环约10年后分离出来的。共获得45个逃逸突变体。他们的HA基因测序在两个关键抗原区域(160环和190螺旋)的四个位点上发现了六个氨基酸替换,特别是N165Y, N165S, K167R,以及160环中164和165残基之间的天冬酰胺插入;和K203R和K203N在190螺旋(编号基于B/Brisbane/60/2008 HA序列)。血球凝集抑制(HI)实验显示,两种单克隆抗体影响了160环突变体和203环突变体的结合。160环突变不影响抗血清对亲本B/爱知/20/99菌株的反应性,而K203N取代降低了抗血清反应性,表明该残基具有重要的抗原性。对1997年至2021年间分离的8株B/Victoria谱系菌株进行的进一步HI分析显示,所有3种单克隆抗体与2016年之后分离的菌株都失去了反应性,而抗血清的反应性降低。值得注意的是,目前的疫苗株B/Austria/1359417/2021在150和203位上有取代,反应性也有所下降。这些发现表明,在B/维多利亚谱系中,150环和190螺旋构成抗原优势位点,有助于免疫逃逸和漂移变异的出现。
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引用次数: 0
The association between influenza infection and acute myocardial infarction: A comprehensive systematic review and meta-analysis 流感感染与急性心肌梗死之间的关系:一项全面的系统回顾和荟萃分析。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-09 DOI: 10.1016/j.virusres.2025.199594
Xia Zhou , Li Feng
Influenza infection could be associated with several systemic complications, including acute myocardial infarction (AMI); however, evidence on this association remains inconsistent. This systematic review and meta-analysis examined the influenza-AMI link, temporal AMI risk post-infection, and in-hospital outcomes and mortality in influenza-infected AMI patients. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science. Observational studies and self-controlled case series (SCCS) designs, were included. Data were extracted and analyzed using random-effects models to calculate pooled odds ratios (ORs), incidence rate ratios (IRRs), and 95 % confidence intervals (CIs). Subgroup analyses were performed based on exposure definitions (laboratory-confirmed influenza vs. influenza-like illness [ILI]), study design, and temporal patterns of AMI risk. In-hospital outcomes, including mortality, complications, length of stay, and costs, were also evaluated. The meta-analysis included 17 studies. A significant association was found, with a pooled adjusted OR of 2.70 (95 % CI: 1.28–5.72). ILI showed a stronger association with AMI (aOR: 2.04; 95 % CI: 1.33–3.14) compared to laboratory-confirmed influenza. Temporal analyses from SCCS studies revealed a markedly increased risk of AMI within the first week post-infection, peaking in days 1–3 (IRR: 6.83; 95 % CI: 4.66–10.01) and gradually declining thereafter. Influenza-infected AMI patients had significantly worse in-hospital outcomes, including higher mortality (OR: 1.60; 95 % CI: 1.55–1.66), and multiorgan failure (OR: 2.90; 95 % CI: 2.79–3.01). Additionally, these patients experienced longer median hospital stays (8.8 days vs. 5.5 days) and higher hospitalization costs ($20,678 vs. $18,269) compared to non-influenza AMI patients. This study confirms a strong link between influenza and AMI, especially early post-infection. Influenza-infected AMI patients experience worse outcomes, longer hospital stays, and higher costs. These findings highlight the importance of influenza prevention strategies, including vaccination, particularly in high-risk groups, to reduce AMI risk and its cardiovascular burden.
流感感染可能与几种全身并发症有关,包括急性心肌梗死(AMI);然而,这种关联的证据仍然不一致。本系统综述和荟萃分析检查了流感与AMI的联系、感染后AMI的时间风险、流感感染AMI患者的住院结局和死亡率。我们对PubMed、EMBASE、Cochrane Library、Scopus和Web of Science进行了系统的检索。包括观察性研究和自我控制病例系列(SCCS)设计。提取数据并使用随机效应模型进行分析,计算合并优势比(ORs)、发病率比(IRRs)和95%置信区间(ci)。亚组分析基于暴露定义(实验室确认的流感vs.流感样疾病[ILI])、研究设计和AMI风险的时间模式。还评估了住院结果,包括死亡率、并发症、住院时间和费用。荟萃分析包括17项研究。两者之间存在显著相关性,合并校正OR为2.70 (95% CI: 1.28-5.72)。ILI与AMI有较强的相关性(aOR: 2.04;95% CI: 1.33-3.14),与实验室确诊的流感相比。SCCS研究的时间分析显示,感染后第一周内AMI的风险显著增加,在第1-3天达到高峰(IRR: 6.83;95% CI: 4.66-10.01),此后逐渐下降。流感感染的急性心肌梗死患者的住院结果明显更差,包括更高的死亡率(OR: 1.60;95% CI: 1.55-1.66)和多器官衰竭(OR: 2.90;95% ci: 2.79-3.01)。此外,与非流感AMI患者相比,这些患者的中位住院时间更长(8.8天对5.5天),住院费用更高(20,678美元对18,269美元)。这项研究证实了流感和急性心肌梗死之间的密切联系,尤其是感染后早期。流感感染的急性心肌梗死患者预后较差,住院时间较长,费用较高。这些发现强调了流感预防策略的重要性,包括疫苗接种,特别是在高危人群中,以减少AMI风险及其心血管负担。
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引用次数: 0
Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients 肝细胞癌患者晚期HCV肝病特征分子谱的验证
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2025-06-07 DOI: 10.1016/j.virusres.2025.199593
In-Woo Park, Hope K. Fiadjoe, Tamara Hoteit, Pankaj Chaudhary
Our previous transcriptome analysis revealed that hepatitis C virus (HCV) infection in hepatocytes regulates the expression of numerous hepatocellular genes in a liver disease stage-specific manner. Based on the fold changes at different stages and the known relevant function of the cellular genes with respect to hepatocellular carcinoma (HCC) and through comprehensive examination with various in silico assays, such as heatmap and volcano analysis for the differential expression, the Cancer Genome Atlas - Hepatocellular Carcinoma (TCGA-HCC) analysis, and molecular approaches, such as qRT-PCR, immunoblot analyses, we have chosen the two up-regulated genes - aldo-keto reductase family 1 member B10 (AKR1B10) and hexokinase domain containing 1 (HKDC1), and two down-regulated genes - glycine N-methyltransferase (GNMT) and C-type lectin domain family 4, member M (CLEC4M), and validated their differential expressions of the genes at disparate stages of liver disease with respect to the development of potential therapeutic targets against HCV-mediated hepatocellular carcinoma (HCC). These data suggested that the differentially expressed genes at various stages could serve as prognostic and diagnostic markers for liver disease progression and may also be utilized in developing therapeutic drugs.
我们之前的转录组分析显示,肝细胞中的丙型肝炎病毒(HCV)感染以肝脏疾病阶段特异性的方式调节许多肝细胞基因的表达。基于肝细胞癌(HCC)在不同阶段的fold变化和已知的细胞基因的相关功能,通过各种计算机分析,如热图和火山分析的差异表达,癌症基因组图谱-肝细胞癌(TCGA-HCC)分析,以及分子方法,如qRT-PCR,免疫印迹分析,我们选择了两个上调基因——醛酮还原酶家族1成员B10 (AKR1B10)和己糖激酶结构域1 (HKDC1),以及两个下调基因——甘氨酸n-甲基转移酶(GNMT)和c型凝集素结构域家族4成员M (CLEC4M),并验证了它们在肝脏疾病不同阶段的差异表达,以开发针对hcv介导的肝细胞癌(HCC)的潜在治疗靶点。这些数据表明,不同阶段的差异表达基因可以作为肝脏疾病进展的预后和诊断标记,也可以用于开发治疗药物。
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引用次数: 0
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Virus research
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