parvovirus B19

细小病毒 B19
  • 文章类型: Journal Article
    大蛋白的结构域和肽的光谱研究是复杂的,因为短肽在水生缓冲液中形成寡聚体的趋势,但是肽与载体蛋白的结合可能会有所帮助。在这项研究中,我们批准了来自VP1细小病毒B19衣壳蛋白的磷脂酶A2结构域的SK30肽片段(残基:144-159;164;171-183;序列:SAVDSAARIHDFRYSQLAKLGINPYTHWTVADEELLKNIK)在酸性介质中从无规卷曲变成α螺旋(如果它与BSA末端残基通过额外的N偶联,把它变成CSK31肽,和SMCC接头)根据CD光谱学结果。相比之下,未缀合的SK30肽不经历这种转变,因为它形成由分子间反平行β折叠连接的稳定寡聚体,根据红外光谱,CD-光谱学,蓝色天然凝胶电泳和离心超滤,as,可能,VP1蛋白的整个分离的磷脂酶结构域。然而,作为长VP1衣壳蛋白的一部分,磷脂酶结构域可能会在内溶酶体中培养基酸化过程中,通过质子化的His153和Asp175之间形成接触的方式改变其折叠,从而促进其N末端部分从无规卷曲向α螺旋的转变。这项研究开辟了疫苗开发的前景,由于兔针对CSK31肽与BSA缀合物的多克隆抗体,其中应该复制磷脂酶A2结构域的第二个α螺旋的结构,可以结合VP1细小病毒B19衣壳的完整重组独特部分的表位(残基:1-227)。
    Spectroscopic studies on domains and peptides of large proteins are complicated because of the tendency of short peptides to form oligomers in aquatic buffers, but conjugation of a peptide with a carrier protein may be helpful. In this study we approved that a fragment of SK30 peptide from phospholipase A2 domain of VP1 Parvovirus B19 capsid protein (residues: 144-159; 164; 171-183; sequence: SAVDSAARIHDFRYSQLAKLGINPYTHWTVADEELLKNIK) turns from random coil to alpha helix in the acidic medium only in case if it had been conjugated with BSA (through additional N-terminal Cys residue, turning it into CSK31 peptide, and SMCC linker) according to CD-spectroscopy results. In contrast, unconjugated SK30 peptide does not undergo such shift because it forms stable oligomers connected by intermolecular antiparallel beta sheet, according to IR-spectroscopy, CD-spectroscopy, blue native gel electrophoresis and centrifugal ultrafiltration, as, probably, the whole isolated phospholipase domain of VP1 protein does. However, being a part of the long VP1 capsid protein, phospholipase domain may change its fold during the acidification of the medium in the endolysosome by the way of the formation of contacts between protonated His153 and Asp175, promoting the shift from random coil to alpha helix in its N-terminal part. This study opens up a perspective of vaccine development, since rabbit polyclonal antibodies against the conjugate of CSK31 peptide with BSA, in which the structure of the second alpha helix from the phospholipase A2 domain should be reproduced, can bind epitopes of the complete recombinant unique part of VP1 Parvovirus B19 capsid (residues: 1-227).
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  • 文章类型: Journal Article
    从汇集的血浆制造的因子VIII和IX凝血因子浓缩物在1970年代和1980年代已被鉴定为血友病(PWHs)患者的有效病毒感染源。为了调查这一时期病毒的范围和多样性,我们分析了24种血液传播病毒的凝血因子浓缩物。核酸是从14种商业生产的凝血因子和10种无偿捐献者中提取的,以冻干形式保存(有效期:1974-1992年)。凝血因子通过商业和内部定量PCR检测血源性病毒甲型肝炎,B,C和E病毒(HAV,HBV,HCV,HEV),HIV-1/2型,细小病毒B19V和PARV4,以及人类pegivirus1和2型(HPgV-1,-2)。HCV和HPgV-1是最常见的检测病毒(14/24测试)主要在商业凝血因子,在1970年代末-1985年,病毒载量经常极高,HCV基因型范围也各不相同。引入病毒灭活后,检测频率急剧下降。HIV-1,HBV,和HAV的检出频率较低(分别为3/24、1/24和1/24);无HEV阳性。相反,在整个研究期间检测到B19V和PARV4,即使在引入干热处理后,与20世纪90年代初正在进行的有据可查的传输到PWHs是一致的。虽然在英国和其他地方,血友病治疗现在主要基于重组因子VIII/IX,对历史血浆来源的凝血因子的全面筛选表明,在整个1970年代至1990年代初,PWHs广泛暴露于血液传播病毒,以及影响凝血因子污染的流行病学和制造参数。
    Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992). Clotting factors were tested by commercial and in-house quantitative PCRs for blood-borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV- types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV-1,-2). HCV and HPgV-1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s-1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV-1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma-derived clotting factors reveals extensive exposure of PWHs to blood-borne viruses throughout 1970s-early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination.
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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
    细小病毒B19(B19V)是一种人类病原体,是婴儿和成人几种疾病的病原体。由于缺乏针对这种病毒的抗病毒药物,治疗方案有限。B19V的次要衣壳蛋白具有独特的N末端,命名为VP1u,这对感染至关重要。VP1u编码受体结合域(RBD),宿主细胞进入所必需的,和磷脂酶A2(PLA2)结构域,对于细胞运输过程中的内体逃逸至关重要。这两个领域都是感染不可或缺的,使RBD成为B19V抑制剂的合理药物靶标,因为它位于病毒的外表面。迄今为止,没有任何细小病毒的VP1u组件的实验性结构信息。在这里,我们报告了B19V的RBD的主链NMR共振分配,并证明了它形成了稳定的结构。主链化学位移与AlphaFold预测的结构非常吻合,验证RBD包含通过紧密转弯连接的三个螺旋。这种RBD构建体现在可以用于进一步的NMR研究,包括全长VP1u的赋值,蛋白质-蛋白质相互作用界面的测定,以及RBD域特异性B19抗病毒药物的开发。数据库:BMRB提交代码:52440。
    Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA2) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain. Database: BMRB submission code: 52440.
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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
    在法国,在96份样本中检测献血者的细小病毒B19(B19V)DNA,以便在血浆中病毒载量较高时丢弃血浆进行分级分离.2015年1月至2024年3月,在COVID-19大流行期间,B19V阳性捐赠减少,随后在2023年强劲反弹,在2023/24年冬季出现异常高的流通量(2023年12月至2024年3月与大流行前相比增加了10倍)。随时间的变化可能与为限制SARS-CoV-2传播而实施的措施有关。
    In France, blood donations are tested in pools of 96 samples for parvovirus B19 (B19V) DNA to discard plasma for fractionation when it contains high viral loads. Between January 2015 and March 2024, B19V-positive donations decreased during the COVID-19 pandemic, followed by a strong rebound in 2023 and unusually high circulation during winter 2023/24 (ca 10 times higher December 2023-March 2024 vs the pre-pandemic period). Variations over time are probably related to measures implemented to limit SARS-CoV-2 spread.
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  • 文章类型: Journal Article
    一名13岁女孩在4周前进行了肾脏移植,有10天的疲劳史,苍白,和头痛。在体检时,注意到心动过速和苍白。实验室检查为严重贫血和轻度白细胞减少症和血小板减少症。EB病毒(EBV)和巨细胞病毒(CMV)的聚合酶链反应(PCR)测试为阴性,细小病毒B19(PVB19)为阳性。尽管免疫抑制和静脉注射免疫球蛋白(IVIG)降低,但它持续了15个月,需要频繁的红细胞输血。PVB19是一种不太常见但显著的并发症。患者的临床过程证明了这种并发症的重要性及其管理方面的挑战。关于肾移植后PVB19引起的复发性贫血的标准化治疗方案,文献中存在明显的空白。这种情况表明需要进一步的研究和共识,以指导类似病例的有效临床干预。
    A 13-year-old girl who had a kidney transplant four weeks prior presented with a 10-day history of fatigue, paleness, and headache. On physical examination, tachycardia and paleness were noted. Laboratory testing was notable for severe anemia and mild leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) test for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative and for parvovirus B19 (PVB19) was positive. Despite lower immunosuppression and administration of intravenous immunoglobulin (IVIG) it persisted for 15 months, and frequent red blood cell transfusions were needed. PVB19 is a less common but significant complication. The patient\'s clinical course demonstrates the importance of this complication and the challenges in its management. A notable void exists in the literature regarding standardized treatment protocols for PVB19-induced recurrent anemia after kidney transplant. This case indicates the need for further research and consensus to guide effective clinical interventions in similar cases.
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  • 文章类型: Journal Article
    背景:未成熟和受抑制的免疫反应使移植儿童成为细小病毒B19(PVB19)的特殊易感人群。然而,移植患儿PVB19感染的临床特征尚未全面描述。
    方法:我们检索了2020年10月1日至2023年5月31日在复旦大学附属儿童医院就诊的所有移植受者的病历,并回顾了移植患儿中PVB19感染病例的医学文献。
    结果:我院201例移植患儿共发现10例PVB19感染,并显示了这些病例的医疗记录。此外,我们从文献中检索到40例移植儿童PVB19感染病例,因此总结了总共50例PVB19感染的独特病例。首次阳性PVB19DNA检测的中位时间为移植后14周。PVB19IgM和IgG仅在26%和24%的儿童中检测到,分别。移植物丢失/功能障碍的发生率高达36%。造血干细胞移植(HSCT)受者显示更高的PVB19负荷,较低的HGB水平,更大的血小板损伤,较低的PVB19IgM/IgG阳性率,与实体器官移植(SOT)接受者相比,移植物功能障碍更多,表明免疫系统更加无能。
    结论:与已发表的成体移植数据相比,移植患儿在PVB19感染后表现出明显的临床特征,包括较低的PVB19IgM/IgG阳性率,更多的移植物功能障碍,以及对造血细胞系的更广泛的损害,这在HSCT接受者中更为突出,因此应该引起更大的关注。
    The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven\'t been comprehensively described.
    We searched the medical records of all the transplant recipients who attended the Children\'s Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children.
    A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system.
    Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.
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  • 文章类型: Journal Article
    细小病毒B19是一个小(26nm),无包裹,单链DNA(5.6kb)病毒。细小病毒B19的唯一已知宿主是人类。细小病毒B19对集落和爆发形成单位的红系前体细胞具有直接细胞毒性。人细小病毒B19是免疫受损个体中感染性红斑和慢性纯红细胞发育不全的病原体。免疫功能低下患者应怀疑急性细小病毒B19感染,患有网织红细胞减少性溶血性贫血和血小板减少症的患者。静脉免疫球蛋白(IVIg)是细小病毒诱导的血细胞减少症的标准治疗方法。我们报告了两例肾移植后出现网织红细胞减少性贫血并被发现患有细小病毒感染的病例。他们对静脉注射丙种球蛋白的常规治疗没有反应。两名患者均接受了利妥昔单抗治疗,其临床和血液学参数均有所改善。以前没有使用利妥昔单抗治疗肾移植后细小病毒引发的自身免疫性溶血性贫血的文献。这篇文章说明了利妥昔单抗将如何在这种情况下有所帮助,当然,这是一个新的想法,但需要进一步的研究和验证。
    Parvovirus B19 is a small (26 nm), nonenveloped, single-stranded DNA (5.6-kb) virus. The only known host for parvovirus B19 is humans. Parvovirus B19 is directly cytotoxic to erythroid precursor cells of the colony- and burst-forming units. Human parvovirus B19 is the etiologic agent of erythema infectiosum and chronic pure red cell aplasia in immunocompromised individuals. Acute parvovirus B19 infection should be suspected in immunocompromised patients, who present with reticulocytopenic hemolytic anemia and thrombocytopenia. Intravenous immunoglobulin (IVIg) is the standard treatment for parvovirus-induced cytopenias. We report two cases of postrenal transplant who presented with reticulocytopenic anemia and were found to have parvovirus infection. They did not respond to conventional treatment with intravenous gamma globulin. Both patients were treated with rituximab with which they had improvement in clinical and hematological parameters. There was no previous documentation of using rituximab in the treatment of parvovirus-triggered autoimmune hemolytic anemia postrenal transplant patients. This article illustrates how rituximab will be helpful in this setting, of course, it is a new thought but requires further studies and validation.
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  • 文章类型: Journal Article
    目标:在加拿大,对送去分级分离的血浆进行细小病毒B19(B19V)和甲型肝炎病毒(HAV)的检测。这项研究比较了加拿大血浆样本中COVID-19限制时代(2015年至2020年2月底[Q1]2020年)和COVID-19限制时代后的B19和HAV核酸检测(NAT)阳性率。
    方法:使用ProcleixPanther系统(Grifols诊断解决方案公司,圣地亚哥,CA,美国)用于B19V和HAV检测。通过单独的样品测试解决了反应池。
    结果:在2015年1月1日至2022年3月31日之间,对来自加拿大血浆供体的3,928,619份标本进行了B19V测试。在同一时期,对3,922,954个样本进行了HAV测试。考虑到样本测试的滞后长达24个月,数据分为:(1)大流行前时期(2015年1月1日至2020年3月31日;B19V测试n=2,412,701,B19VNAT阳性n=240[0.01%],HAV测试n=2,407,036,HAVNAT阳性n=26[0.001%]);(2)两年混合影响期(2020年4月1日至2022年3月31日;B19V测试n=968,250,B19VNAT阳性n=14[0.001%],HAV测试n=968,250,HAVNAT阳性n=2[0.0002%]);和(3)大流行影响期(2022年4月1日至3月31日,2023年;B19V测试n=597,668,B19VNAT阳性n=3[0.0005%],HAV测试n=597,668,HAVNAT阳性n=1[0.0002%])。
    结论:从大流行前到大流行影响期,B19V和HAV阳性捐赠的百分比显着降低。
    OBJECTIVE: In Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre-COVID-19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post-COVID-19 restriction era.
    METHODS: Pooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing.
    RESULTS: Between 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre-pandemic period (1 January 2015-31 March 2020; B19V tested n = 2,412,701, B19V NAT-positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT-positive n = 26 [0.001%]); (2) a two-year mixed-impact period (1 April 2020-31 March 2022; B19V tested n = 968,250, B19V NAT-positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT-positive n = 2 [0.0002%]); and (3) a pandemic-impact period (1 April 2022-31 March, 2023; B19V tested n = 597,668, B19V NAT-positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT-positive n = 1 [0.0002%]).
    CONCLUSIONS: The percentage of B19V- and HAV-positive donations was significantly reduced from the pre-pandemic period to the pandemic-impact period.
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