Parvoviridae Infections

细小病毒科感染
  • 文章类型: Journal Article
    腺相关病毒(AAV)是有前途的基因治疗载体,但是当用预先存在的中和抗体治疗患者时,就会出现挑战。全球血清阳性率研究提供了不同人群中现有免疫的快照。由于巴斯克地区社会地理景观的独特性,我们调查了巴斯克地区居民中8种AAV血清型的血清阳性率。我们发现AAV3的血清阳性率最高,AAV9的血清阳性率最低。此外,不到50%的巴斯克人群具有抗AAV4,AAV6和AAV9的中和抗体.我们的发现为巴斯克地区的AAV感染提供了见解,公共卫生,以及基于AAV的疗法的发展。
    Adeno-associated viruses (AAVs) are promising gene therapy vectors, but challenges arise when treating patients with preexisting neutralizing antibodies. Worldwide seroprevalence studies provide snapshots of existing immunity in diverse populations. Owing to the uniqueness of the Basque socio-geographical landscape, we investigated the seroprevalence of eight AAV serotypes in residents of the Basque Country. We found the highest seroprevalence of AAV3, and the lowest seroprevalence of AAV9. Additionally, less than 50% of the Basque population has neutralizing antibodies against AAV4, AAV6, and AAV9. Our findings provide insight into AAV infections in the Basque region, public health, and the development of AAV-based therapeutics.
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  • 文章类型: Journal Article
    背景:犬细小病毒2型(CPV-2)是感染犬的最常见的肠道病毒。CPV是主要由狗的临床胃肠道体征定义的传染病的病原体。在1970年代后期,CPV-2是一种能够感染家犬并在世界各地生长的新病毒。VP2基因是致病性的关键决定因素,抗原性,和CPV-2的宿主相互作用。
    目的:VP2基因的分子特征对于了解CPV进化和流行病学至关重要。
    方法:对编码VP2蛋白的基因进行测序并与全世界的参考菌株进行比较。最大似然法用于使用CPVVP2基因核苷酸序列构建系统发育树。
    结果:我们对VP2基因的系统发育分析显示,5个菌株非常相似,并且聚集在一起,三个菌株在2b进化枝中,而其他两个在2a/2b进化枝。
    结论:本文报道了两种新型CPV-2a/2b亚型在有胃肠道症状的犬中的分子特征。在包含编码结构蛋白VP2的开放阅读框(ORF)之一的CPV基因组区域上进行遗传分析。序列分析表明新的和未报告的序列变化,主要影响VP2基因,其中包括突变Ser297Ala和Leu87Met。这项研究代表了Türkiye中新的CPV-2a/2b亚型的第一个证据。由于VP2在编码CPV-2的衣壳蛋白中的关键作用及其在宿主-病毒相互作用中的重要参与,密切监测其进化变化并在寻找新的或预先存在的亚型时保持谨慎至关重要.
    结论:这项研究强调了连续分子研究对于获得有关新型CPV突变体循环的更多见解的重要性。
    BACKGROUND: Canine parvovirus type 2 (CPV-2) is the most common enteric virus that infects canids. CPV is the causative agent of a contagious disease defined mostly by clinical gastrointestinal signs in dogs. During the late 1970s, CPV-2 emerged as a new virus capable of infecting domestic dogs and growing across the world. The VP2 gene stands out as a key determinant in the pathogenicity, antigenicity, and host interactions of CPV-2.
    OBJECTIVE: The molecular characterization of the VP2 gene is crucial for understanding CPV evolution and epidemiology.
    METHODS: Genes encoding the VP2 protein were sequenced and compared to reference strains worldwide. The maximum likelihood method was used to build a phylogenetic tree using CPV VP2 gene nucleotide sequences.
    RESULTS: Our phylogenetic analysis of the VP2 gene revealed that five strains were very similar and clustered together, and three strains were in the 2b clade, whereas the other two were in the 2a/2b clade.
    CONCLUSIONS: This paper reports the molecular characterization of two novel CPV-2a/2b subtypes in dogs with gastrointestinal symptoms. Genetic analysis was conducted on a CPV genomic region encompassing one of the open reading frames (ORFs) encoding the structural protein VP2. Sequence analysis indicates new and unreported sequence changes, mainly affecting the VP2 gene, which includes the mutations Ser297Ala and Leu87Met. This study represents the first evidence of a new CPV-2a/2b subtype in Türkiye. Due to VP2\'s crucial role in encoding the capsid protein of CPV-2 and its significant involvement in the host-virus interaction, it is critical to closely monitor its evolutionary changes and be cautious while searching for novel or pre-existing subtypes.
    CONCLUSIONS: This study highlights the significance of continuous molecular research for acquiring more insights on the circulation of novel CPV mutants.
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  • 文章类型: Case Reports
    A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.
    患者男性,19岁,高危急性B淋巴细胞白血病行单倍体异基因造血干细胞移植,移植后多次出现贫血,检测血细小病毒B19核酸阳性,随后出现冷凝集素综合征、多器官功能障碍(呼吸衰竭、肝脏损害等)。在病毒感染和冷凝集素综合征治疗矛盾情况下充分给予支持治疗、应用补体抑制剂控制溶血、坚持抗病毒治疗,适时加用糖皮质激素及免疫抑制剂,最终获得了较好的治疗效果。.
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  • 文章类型: Journal Article
    猪细小病毒(PPV)是全世界猪繁殖失败的最重要因素之一。PPV包括归因于四个属的八个遗传上不同的物种:原病毒(PPV1,PPV8),四联病毒(PPV2-3),Copipavovirus(PPV4-6),和查巴病毒(PPV7)。2016年,PPV7首先在美国和欧洲被检测到,亚洲,和南美洲。最近,在意大利的养猪场也发现了繁殖障碍。这项研究旨在评估PPV7在撒丁岛的家猪和野猪中的循环,意大利。此外,分析了其与猪圆环病毒2(PCV2)和3(PCV3)的共感染,和PPV7意大利菌株进行分子表征。在家猪中检测到PPV7,第一次,意大利的野猪在20.59%的家猪和野猪样品中检测到PPV7病毒基因组。PPV7检测在家猪中显著降低,PPV7阳性猪的PCV2/PCV3共感染率高于PPV7阴性猪。NS1基因的分子表征显示出非常高的重组频率,这可能会促进病毒传播。
    Porcine parvoviruses (PPVs) are among the most important agents of reproductive failure in swine worldwide. PPVs comprise eight genetically different species ascribed to four genera: Protoparvovirus (PPV1, PPV8), Tetraparvovirus (PPV2-3), Copiparvovirus (PPV4-6), and Chaphamaparvovirus (PPV7). In 2016, PPV7 was firstly detected in the USA and afterwards in Europe, Asia, and South America. Recently, it was also identified in Italy in pig farms with reproductive failure. This study aimed to evaluate the circulation of PPV7 in domestic and wild pigs in Sardinia, Italy. In addition, its coinfection with Porcine Circovirus 2 (PCV2) and 3 (PCV3) was analysed, and PPV7 Italian strains were molecularly characterised. PPV7 was detected in domestic pigs and, for the first time, wild pigs in Italy. The PPV7 viral genome was detected in 20.59% of domestic and wild pig samples. PPV7 detection was significantly lower in domestic pigs, with higher PCV2/PCV3 co-infection rates observed in PPV7-positive than in PPV7-negative domestic pigs. Molecular characterisation of the NS1 gene showed a very high frequency of recombination that could presumably promote virus spreading.
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  • 文章类型: Journal Article
    在过去的十年中,许多国家都出现了新发现的马肝性黄病毒和细小病毒的报告,这一发现激发了大量的兴趣和临床研究。尽管通常在没有疾病迹象的马中发现,马细小病毒肝炎(EqPV-H)和马肝炎病毒(EqHV)与肝脏疾病相关,包括在施用污染的抗毒素之后。我们的目的是确定澳大利亚马匹中是否存在EqPV-H和EqHV,以及法国马匹中是否存在EqPV-H,并检查全球两侧受感染马匹中两种病毒株之间的序列多样性。收集了来自188匹澳大利亚马和256匹法国马的血清,这些马具有和没有临床疾病迹象。256匹(4.7%)中的12匹和188匹(3.2%)法国和澳大利亚马匹中的6匹,分别,对EqPV-H的分子检测呈阳性。256匹(1.9%)中的五匹和188匹(11.2%)法国和澳大利亚马匹中的21匹,分别,对EqHV的分子检测呈阳性。这两种病毒的澳大利亚毒株都是基因组聚集的,与法国马的菌株相反,分布更广泛。这项初步调查的结果,随着EqHV和EqPV-H在澳大利亚和法国的分子检测,增加了人们对这些最近发现的嗜肝病毒的认识。它不仅在地理地方性方面提供了有价值的信息,而且将指导马临床医生,看护者,以及有关传染因子和同种异体组织污染的潜在影响的当局。尽管我们已经填补了世界地图上关于马嗜肝病毒的许多空白,这一新兴领域的进一步前瞻性研究可能有助于阐明这些病原体的危险因素和发病机制,并有助于预防和诊断方面的病例管理.
    Reports of newly discovered equine hepatotropic flavi- and parvoviruses have emerged throughout the last decade in many countries, the discovery of which has stimulated a great deal of interest and clinical research. Although commonly detected in horses without signs of disease, equine parvovirus hepatitis (EqPV-H) and equine hepacivirus (EqHV) have been associated with liver disease, including following the administration of contaminated anti-toxin. Our aim was to determine whether EqPV-H and EqHV are present in Australian horses and whether EqPV-H was present in French horses and to examine sequence diversity between strains of both viruses amongst infected horses on either side of the globe. Sera from 188 Australian horses and 256 French horses from horses with and without clinical signs of disease were collected. Twelve out of 256 (4.7%) and 6 out of 188 (3.2%) French and Australian horses, respectively, were positive for the molecular detection of EqPV-H. Five out of 256 (1.9%) and 21 out of 188 (11.2%) French and Australian horses, respectively, were positive for the molecular detection of EqHV. Australian strains for both viruses were genomically clustered, in contrast to strains from French horses, which were more broadly distributed. The findings of this preliminary survey, with the molecular detection of EqHV and EqPV-H in Australia and the latter in France, adds to the growing body of awareness regarding these recently discovered hepatotropic viruses. It has provided valuable information not just in terms of geographic endemicity but will guide equine clinicians, carers, and authorities regarding infectious agents and potential impacts of allogenic tissue contamination. Although we have filled many gaps in the world map regarding equine hepatotropic viruses, further prospective studies in this emerging field may be useful in terms of elucidating risk factors and pathogenesis of these pathogens and management of cases in terms of prevention and diagnosis.
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  • 文章类型: Journal Article
    从2023年4月到2024年5月,法国发生了细小病毒B19(B19V)感染的异常流行。2019年B19VIgM阳性血清学数量比上次疫情高4倍。来自急诊网络的临床数据证实了这一观察结果。通过所有数据源观察到儿童的发病率和死亡率后果。在成年人中,仅在实验室确认的数据中观察到增加.医生和决策者应该被告知,以便更好地预防,诊断和管理高危患者。
    From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.
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  • 文章类型: Journal Article
    人类博卡病毒(HBoV)基因组的多样性和进化,导致呼吸道疾病,几乎没有被研究过。这里,我们旨在从2017年至2022年期间(5年7个月)收集的患者鼻咽样本中获取并表征HBoV基因组.下一代测序(NGS)在使用GEMI实施了内部多重PCR扩增策略后,使用了Illumina技术。用CLC基因组学组装和分析基因组,Mafft,BioEdit,MeV,Nextclade,MEGA,还有iTol.共获得213个基因组。系统发育将它们全部分类为Bocavirus1(HBoV1)物种。在研究期间,通过对27个可变基因组位置的层次聚类分析确定的5个HBoV1基因型簇分散在研究期间,尽管年患病率存在差异。检测到总共167个氨基酸取代。此外,在52%的样本中观察到共感染,鼻病毒,然后腺病毒(HAdV)是最常见的病毒。主成分分析表明,HBoV1基因型簇α与HAdV共感染有一定的相关性。随后对HBoV1阳性样品和阴性对照的HAdV分型表明,HAdVC物种占主导地位,但HAdVB与HBoV1显着相关。总的来说,我们在这里描述了为法国测序的第一个HBoV1基因组。HBoV1与HAdVB的相关性值得进一步研究。
    The diversity and evolution of the genomes of human bocavirus (HBoV), which causes respiratory diseases, have been scarcely studied. Here, we aimed to obtain and characterize HBoV genomes from patients\'s nasopharyngeal samples collected between 2017 and 2022 period (5 years and 7 months). Next-generation sequencing (NGS) used Illumina technology after having implemented using GEMI an in-house multiplex PCR amplification strategy. Genomes were assembled and analyzed with CLC Genomics, Mafft, BioEdit, MeV, Nextclade, MEGA, and iTol. A total of 213 genomes were obtained. Phylogeny classified them all as of Bocavirus 1 (HBoV1) species. Five HBoV1 genotypic clusters determined by hierarchical clustering analysis of 27 variable genome positions were scattered over the study period although with differences in yearly prevalence. A total of 167 amino acid substitutions were detected. Besides, coinfection was observed for 52% of the samples, rhinoviruses then adenoviruses (HAdVs) being the most common viruses. Principal component analysis showed that HBoV1 genotypic cluster α tended to be correlated with HAdV co-infection. Subsequent HAdV typing for HBoV1-positive samples and negative controls demonstrated that HAdVC species predominated but HAdVB was that significantly HBoV1-associated. Overall, we described here the first HBoV1 genomes sequenced for France. HBoV1 and HAdVB association deserves further investigation.
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  • 文章类型: Journal Article
    人类博卡病毒1(HBoV1)是一种人类细小病毒,可引起幼儿下呼吸道感染。它包含约5.5kb的单链(ss)DNA基因组,编码140个核苷酸的小非编码RNA,称为博卡病毒编码的小RNA(BocaSR),除了病毒蛋白。这里,我们使用DMS-MaPseq确定了体内BocaSR的二级结构。我们的发现表明,BocaSR在多个位点经历了N6-甲基腺苷(m6A)修饰,这对于分裂的HEK293细胞和人类气道上皮细胞的非分裂细胞中的病毒DNA复制至关重要。机械上,我们发现m6A修饰的BocaSR充当招募Y家族DNA修复DNA聚合酶(Pol)η和Polκ的介质,可能是通过BocaSR与病毒基因组右端病毒DNA复制起点之间的直接相互作用.因此,本报告表示病毒非编码小RNA通过m6A修饰直接参与病毒DNA复制.
    Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5 kb that encodes a small noncoding RNA of 140 nucleotides known as bocavirus-encoded small RNA (BocaSR), in addition to viral proteins. Here, we determined the secondary structure of BocaSR in vivo by using DMS-MaPseq. Our findings reveal that BocaSR undergoes N6-methyladenosine (m6A) modification at multiple sites, which is critical for viral DNA replication in both dividing HEK293 cells and nondividing cells of the human airway epithelium. Mechanistically, we found that m6A-modified BocaSR serves as a mediator for recruiting Y-family DNA repair DNA polymerase (Pol) η and Pol κ likely through a direct interaction between BocaSR and the viral DNA replication origin at the right terminus of the viral genome. Thus, this report represents direct involvement of a viral small noncoding RNA in viral DNA replication through m6A modification.
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  • 文章类型: Journal Article
    我们报告了2024年第一季度丹麦细小病毒B19感染的流行,其峰值发病率是2017年最近一次流行的3.5倍。总的来说,20.1%(130/648)的实验室确诊病例怀孕。在12.3%(16/130)的孕妇中观察到严重的不良结局,包括胎儿贫血,胎儿积水和流产。细小病毒B19感染没有系统监测,但是丹麦目前正在建立一个基于实验室的国家监测系统。
    We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.
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  • 文章类型: Journal Article
    重组番鸭细小病毒(rMDPV)是经典番鸭细小病毒(MDPV)和鹅细小病毒(GPV)之间遗传重组的产物。重组事件发生在位于VP3基因中间的1.1kbDNA片段中,和从P9启动子延伸到Rep1ORF的5'起始区的187bp序列。这导致VP3内五个氨基酸的改变。尽管有这些基因变化,重组和氨基酸突变对rMDPV致病性的确切影响仍然不明确.在这项研究中,基于rMDPV菌株ZW和经典MDPV菌株YY,使用反向遗传技术产生了三种嵌合病毒(rZW-mP9,rZW-mPR187和rYY-rVP3)和五个引入氨基酸突变的突变体(rZW-g5aa和rYY-5aa(ZW))。与亲本病毒rZW相比,rZW-g5aa在含胚鸭蛋中表现出延长的平均死亡时间(MDT)和降低的中位致死剂量(ELD50)。相比之下,与rYY相比,rYY-5aa(ZW)在MDT和ELD50方面没有显着差异。在2日龄的番鸭身上,感染rZW-g5aa和rYY-5aa(ZW)导致的死亡率只有20%和10%,分别,而三种嵌合病毒(rZW-mP9,rZW-mPR187,rYY-rVP3)和rZW的感染仍导致100%的死亡率。值得注意的是,rYY-rVP3,包含来自菌株ZW的VP3区域,6日龄番鸭的死亡率为50%,并表现出明显的水平传播。总的来说,我们的发现表明,VP3中的重组和随之而来的氨基酸变化对番鸭rMDPV的毒力增强具有协同影响。
    Recombinant Muscovy duck parvovirus (rMDPV) is a product of genetic recombination between classical Muscovy duck parvovirus (MDPV) and goose parvovirus (GPV). The recombination event took place within a 1.1-kb DNA segment located in the middle of the VP3 gene, and a 187-bp sequence extending from the P9 promoter to the 5\' initiation region of the Rep1 ORF. This resulted in the alteration of five amino acids within VP3. Despite these genetic changes, the precise influence of recombination and amino acid mutations on the pathogenicity of rMDPV remains ambiguous. In this study, based on the rMDPV strain ZW and the classical MDPV strain YY, three chimeric viruses (rZW-mP9, rZW-mPR187, and rYY-rVP3) and the five amino acid mutations-introduced mutants (rZW-g5aa and rYY-5aa(ZW)) were generated using reverse genetic technology. When compared to the parental virus rZW, rZW-g5aa exhibited a prolonged mean death time (MDT) and a decreased median lethal dose (ELD50) in embryonated duck eggs. In contrast, rYY-5aa(ZW) did not display significant differences in MDT and ELD50 compared to rYY. In 2-day-old Muscovy ducklings, infection with rZW-g5aa and rYY-5aa(ZW) resulted in mortality rates of only 20% and 10%, respectively, while infections with the three chimeric viruses (rZW-mP9, rZW-mPR187, rYY-rVP3) and rZW still led to 100% mortality. Notably, rYY-rVP3, containing the VP3 region from strain ZW, exhibited 50% mortality in 6-day-old Muscovy ducklings and demonstrated significant horizontal transmission. Collectively, our findings indicate that recombination and consequent amino acid changes in VP3 have a synergistic impact on the heightened virulence of rMDPV in Muscovy ducklings.
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