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Short-form thymic stromal lymphopoietin (sfTSLP) restricts herpes simplex virus infection of human primary keratinocytes 短型胸腺基质淋巴细胞生成素(shfTSLP)可抑制人类原代角朊细胞感染单纯疱疹病毒。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-04 DOI: 10.1002/jmv.29865
Jana Zeitvogel, Katinka Döhner, Ilona Klug, Timmy Richardo, Beate Sodeik, Thomas Werfel

Eczema herpeticum (EH) is a disseminated severe herpes simplex virus type 1 (HSV-1) infection that mainly occurs in a subset of patients suffering from atopic dermatitis (AD). EH is complex and multifaceted, involving immunological changes, environmental influences, and genetic aberrations. Certain genetic variants of the thymic stromal lymphopoietin (TSLP) may predispose to develop severe HSV-1-induced eczema. Therefore, we investigated the impact of TSLP on HSV-1 infection. TSLP encodes for two distinct forms: a long-form (lfTSLP), primarily associated with type 2 immunity, and a short-form (sfTSLP) with anti-inflammatory and antimicrobial properties. While sfTSLP reduced HSV-1 infectibility in human primary keratinocytes (HPK), lfTSLP did not. In HPK treated with sfTSLP, HSV-1 gene expression, and replication decreased, while virion binding to cells and targeting of incoming capsids to the nucleus were not diminished compared to untreated cells. sfTSLP caused only minor changes in the expression of innate immunity cytokines, and its inhibition of HSV-1 infection did not require de novo protein synthesis. Time window experiments indicated a different antiviral mechanism than LL-37. sfTSLP showed the strongest antiviral effect when administered to HPK before or after inoculation with HSV-1, and outperformed the inhibitory potential of LL-37 under these conditions. Our data show that sfTSLP has antiviral functions and promotes repression of the HSV-1 infection in HPK.

带状疱疹湿疹(EH)是一种播散性重症单纯疱疹病毒 1 型(HSV-1)感染,主要发生在特应性皮炎(AD)患者中。EH 的发病原因复杂多样,涉及免疫学变化、环境影响和基因畸变。胸腺基质淋巴细胞生成素(TSLP)的某些基因变异可能会诱发严重的 HSV-1 引起的湿疹。因此,我们研究了 TSLP 对 HSV-1 感染的影响。TSLP 编码两种不同的形式:主要与 2 型免疫相关的长型 TSLP(lfTSLP)和具有抗炎和抗菌特性的短型 TSLP(sfTSLP)。sfTSLP 可降低 HSV-1 在人类原代角质细胞(HPK)中的感染性,而 lfTSLP 则不会。在使用 sfTSLP 处理的 HPK 中,HSV-1 基因表达和复制均有所下降,而与未处理的细胞相比,病毒与细胞的结合以及将进入的病毒盖膜靶向细胞核的能力并没有减弱。sfTSLP 只对先天性免疫细胞因子的表达造成轻微变化,而且它对 HSV-1 感染的抑制不需要新的蛋白质合成。时间窗实验表明,sfTSLP 的抗病毒机制与 LL-37 不同。在接种 HSV-1 之前或之后给 HPK 施用 sfTSLP,其抗病毒效果最强,在这些条件下的抑制潜力超过了 LL-37。我们的数据表明,sfTSLP具有抗病毒功能,能促进抑制HPK感染HSV-1。
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引用次数: 0
N121T and N121S substitutions on the SARS-CoV-2 spike protein impact on serum neutralization SARS-CoV-2 棘突蛋白上的 N121T 和 N121S 取代对血清中和的影响。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29871
Van Thi Lo, Hyun A. Lim, Seong Sik Jang, Min Chan Kim, Alain Chrysler Chamfort, Ha Yeon Kim, Da Young Mun, Min Chang Kang, Han Byul Lee, Sunjoo Kim, Younghee Lee, Sangkyu Park, Sun-Woo Yoon, Hye Kwon Kim

The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment. Although N121T and N121S substitutions are not currently major SARS-CoV-2 variants of concern, this study could provide fundamental information to prepare for potential future mutations at the N121 site of SARS-CoV-2.

SARS-CoV-2 尖峰蛋白上的 N121 位点与血红素及其代谢产物胆绿素有关,会影响抗体的结合。N121T 和 N121S 两个置换位点在自然条件下以及在仓鼠的 SARS-CoV-2 和甲型流感病毒双重感染模型中都被观察到。用免疫小鼠和人类血清对携带野生型、N121T 和 N121S 尖峰的 HIV-1 颗粒进行血清假型中和试验发现,N121T 和 N121S 突变对血清中和的影响大于胆绿素处理。尽管 N121T 和 N121S 突变目前还不是令人担忧的 SARS-CoV-2 主要变异,但这项研究可以提供基本信息,为 SARS-CoV-2 N121 位点未来可能发生的突变做好准备。
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引用次数: 0
Retroactive blood-borne pathogens detection of archival clotting factor concentrates throughout the 1970s and 1980s highlights virus contaminations 在整个 20 世纪 70 年代和 80 年代,对档案凝血因子浓缩物进行的血源性病原体追溯检测突显了病毒污染问题。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29907
Morgan Brisse, Hinh Ly
<p>Blood coagulation relies on a cascade of protein-protein interactions that comprise two primary downstream pathways (intrinsic and extrinsic<span><sup>1</sup></span>). Individuals deficient in certain coagulation pathway proteins, also known as clotting factors, may present with primary or secondary bleeding disorders (coagulopathies). For example, hemophilia results from genetic alterations to factors VIII, IX or XI,<span><sup>2</sup></span> while secondary bleeding disorders may result from dysregulation of clotting factors caused by underlying conditions,<span><sup>3-5</sup></span> medication use,<span><sup>6</sup></span> or infection.<span><sup>7-9</sup></span> Concentrated coagulation factors derived from human blood donations have been made available for treating bleeding disorders since the 1970s.<span><sup>10, 11</sup></span> However, therapeutic coagulation-factor use was found in the 1980s to be associated with a significantly increased risk of developing disease from the then newly discovered blood-borne pathogens (BBPs), such as human immunodeficiency virus-1 (HIV-1, discovered in 1983) and hepatitis C virus (HCV, discovered in 1990).<span><sup>12-15</sup></span> Measures were subsequently put into place throughout the mid-to-late 1980s and early 1990s to limit BBP spread to patients, who were using clotting factor products. Those practices included viral detection, viral exclusion and inactivation, and blood donor screening.</p><p>The degree of viral burden carried by clotting factor products before viral exclusion practices remained unknown with regard to contamination with HCV, HIV-1 and/or other BBPs that had since been found in patients with hemophilia (PWHs).<span><sup>16-19</sup></span> The authors of a newly published article in the Journal of Medical Virology<span><sup>20</sup></span> retrospectively identified BBPs present in 24 lyophilized clotting factor samples (14 commercially produced clothing factors and 10 from non-remunerated blood donors) taken from three time periods: 1974–1977, 1981–1985 and 1989–1992. Blood factor products (either single coagulation factor or a combination of the factors) came from commercial and nationalized (British and French blood bank) sources and were sorted by their listed expiration dates (Figure 1), as production date for each of them was not recorded. Using established or in-house developed qPCR assays, the authors intended to test those products for HIV-1, HIV-2, hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV), human pegiviruses 1 and 2 (HPgV1, HPgV2), and the parvoviruses B19V and PARV4. It is important to note that while the authors stated in the abstract that HIV-2 would be part of a panel of BBPs to be tested, they did not report the result of this test in the subsequent sections of the manuscript. It is, therefore, unclear whether this had been done for this study. Regardless, samples identified as positive for HCV or HIV-1
血液凝固依赖于一连串蛋白质与蛋白质之间的相互作用,这包括两个主要的下游途径(内在和外在1)。缺乏某些凝血途径蛋白(又称凝血因子)的人可能会出现原发性或继发性出血性疾病(凝血病)。例如,血友病是由于因子 VIII、IX 或 XI 的基因改变所致,2 而继发性出血性疾病则可能是由于潜在疾病、3-5 药物使用6 或感染导致凝血因子失调所致、11 然而,在 20 世纪 80 年代,人们发现治疗性凝血因子的使用与当时新发现的血液传播病原体(BBP)相关,如人类免疫缺陷病毒-1(HIV-1,1983 年发现)和丙型肝炎病毒(HCV,1990 年发现),这大大增加了患者患病的风险。这些措施包括病毒检测、病毒排除和灭活,以及献血者筛查。病毒排除措施之前,凝血因子产品携带病毒的程度尚不清楚,也不知道血友病患者(PWHs)是否感染了 HCV、HIV-1 和/或其他 BBP。16-19 《医学病毒学杂志》(Journal of Medical Virology)20 上最新发表的一篇文章的作者回顾性地鉴定了从 1974-1977、1981-1985 和 1989-1992 这三个时期采集的 24 份冻干凝血因子样本(14 份商业生产的服装因子和 10 份来自无偿献血者的样本)中存在的 BBP。血液因子产品(单一凝血因子或因子组合)来自商业和国有(英国和法国血库)来源,并按其列出的有效期进行了分类(图 1),因为每种产品的生产日期都没有记录。作者打算使用已有的或内部开发的 qPCR 检测方法,对这些产品进行 HIV-1、HIV-2、甲型肝炎病毒 (HAV)、乙型肝炎病毒 (HBV)、丙型肝炎病毒 (HCV) 和戊型肝炎病毒 (HEV)、人类佩吉病毒 1 和 2 (HPgV1、HPgV2) 以及副病毒 B19V 和 PARV4 的检测。值得注意的是,虽然作者在摘要中指出 HIV-2 将是要测试的 BBPs 小组的一部分,但他们并没有在手稿的后续部分报告这一测试的结果。因此,目前还不清楚这项研究是否进行了这项检测。无论如何,被确定为 HCV 或 HIV-1 阳性的样本都要进行 Illumina 或 Sanger 测序,以检测病毒株,并与这些 BBPs 的历史和当前流行毒株进行比较。不过,作者推断,1974 年至 1975 年的样本可能都没有检测到病毒,因为这一时期用于产品纯化的血浆池较小。HIV-1、HAV 和 HBV 也分别只在 3/24 份、1/24 份和 1/24 份样本中发现。到 1983-1984 年,HCV 水平达到峰值,比 1976 年的水平高出几个对数,1981-1985 年的所有样本中都能检测到,1989 年后只有一个样本中的水平相对较低。两个样本(1983 年和 1985 年)和一个样本(1983 年)中检测到的 HIV-1 水平相对较低,这与 20 世纪 80 年代检测的凝血因子产品中零星出现 HIV-121 的情况一致,也与英国发现血清转换的 PWH 人数最多的时期相吻合。这些发现表明,虽然已知 PWHs 的 HBV 感染率很高,23, 24 但他们额外接触 HAV25, 26 和 HEV 的水平相对较低、31 对阳性样本进行的 Illumina 测序确定了五种 HCV 基因型,这些基因型当时在英国的 PWHs 中均有发现,32-34 这与之前的研究相吻合,研究显示在受影响的 PWHs 中发现的病毒基因型与当地人群中流行的病毒基因型密切相关35。
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引用次数: 0
Plasma vitamin D levels are correlated with the pathogenesis of human T-cell leukemia virus type 1-associated diseases 血浆维生素 D 水平与人类 T 细胞白血病病毒 1 型相关疾病的发病机制有关。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29898
Yasuko Sagara, Hitomi Nakamura, Yasuhiro Sagara, Etsuko Shitsuta, Kaoru Uchimaru, Yoshihisa Yamano, Toshiki Watanabe, Kiyonori Miura, Koji Matsuzaki

The active form of vitamin D (VD) exerts hormonal effects by regulating the expression of genes involved in T-cell activity, cell differentiation, and proliferation. Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of life-threatening diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM). Among ATL patients, hypercalcemia is one of the most serious complications due to bone resorption. In this study, wild-type mice administered UV-irradiated HTLV-1-infected cells showed up to 47% decrease of plasma VD level compared with untreated mice. To clarify the effect of HTLV-1 on plasma VD level, 315 samples registered in nationwide cohort study on ATL onset were measured. The VD level in HAM (14.98 ± 8.5 ng/mL) was significantly lower than those in asymptomatic carriers and ATL (p < 0.05). Upon comparing the VD levels in ATL stratified by disease subtypes, acute ATL showed a lower level (15.81 ± 12.0 ng/mL) than chronic and smoldering types (p < 0.05). In the longitudinal observation, VD levels were significantly higher in untreated spontaneous remission cases than in ATL progression cases, in which the VD levels decreased approximately 40% after onset. In cases of relapse after transplantation, the plasma VD level dropped to 38.7% of the pre-relapse level, while in cases of complete remission, the VD level increased with improvement of the performance status. Taken together, these results suggest that plasma VD level is a potential indicator for the onset and relapse of HTLV-1-associated diseases.

维生素 D (VD) 的活性形式通过调节参与 T 细胞活性、细胞分化和增殖的基因的表达来发挥激素作用。人类 T 细胞白血病病毒 1 型(HTLV-1)是威胁生命的疾病--成人 T 细胞白血病(ATL)和 HTLV-1 相关骨髓病(HAM)的致病因子。在 ATL 患者中,高钙血症是骨吸收导致的最严重并发症之一。在这项研究中,给野生型小鼠注射经紫外线照射的 HTLV-1 感染细胞后,其血浆 VD 水平比未经处理的小鼠下降了 47%。为了明确 HTLV-1 对血浆 VD 水平的影响,我们对全国范围内有关 ATL 发病的队列研究中登记的 315 个样本进行了测量。HAM的VD水平(14.98 ± 8.5 ng/mL)明显低于无症状携带者和ATL(p
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引用次数: 0
Criteria for second generation comparator tests in validation of novel HPV DNA tests for use in cervical cancer screening 用于宫颈癌筛查的新型 HPV DNA 检测验证中的第二代对比检测标准。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29881
Marc Arbyn, Kate Cuschieri, Jesper Bonde, Rob Schuurman, Clementina Cocuzza, Davy Vanden Broeck, Fang-Hui Zhao, Remila Rezhake, Murat Gultekin, Silvia de Sanjosé, Karen Canfell, David Hawkes, Marion Saville, Peter Hillemanns, Joakim Dillner, Johannes Berkhof, Jean-Luc Prétet, Tarik Gheit, Gary Clifford, Partha Basu, Maribel Almonte, Nicolas Wentzensen, Mario Poljak

While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.

虽然 HC2 和 GP5+/6+ PCR-EIA 在新 HPV 检测方法的测试验证中发挥了关键作用,但它们代表了基于不再广泛使用的技术的第一代参照测试。在本指南中,提出了第二代对比试验的标准,包括更详细地解析 HPV 基因型。第二代对比试验应只优先针对被列为致癌的 12 种基因型(IARC-I 组),并在至少三项验证研究中显示,与第一代对比试验相比,CIN2+ 和 CIN3+ 的灵敏度和≤CIN1 的特异性一致,相对灵敏度基准为 0.95,相对特异性基准为 0.98。验证应考虑所用的储存介质和其他样本处理程序。为确定符合这些严格标准的检测方法,我们进行了元分析。有四项检测符合新标准:(1) RealTime 高危 HPV 检测(雅培公司);(2) Cobas-4800 HPV 检测(罗氏分子系统公司);(3) Onclarity HPV 检测(BD 诊断公司);(4) Anyplex II HPV HR 检测(Seegene 公司)。这四种检测方法针对 14 种致癌基因型,前两种检测方法分别识别 HPV16 和 18 型,第三种检测方法分别识别五种类型,第四种检测方法分别识别所有类型。
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引用次数: 0
Epidemiological and clinical overview of the 2024 Oropouche virus disease outbreaks, an emerging/re-emerging neurotropic arboviral disease and global public health threat 2024 年奥罗普切病毒病爆发的流行病学和临床概况,这是一种新发/再发神经性虫媒病毒病,对全球公共卫生构成威胁。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29897
Benjamin M. Liu
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引用次数: 0
Clinical impact of recent surge in acute parvovirus B19 infections in Leicester UK, March–July 2024 2024 年 3 月至 7 月英国莱斯特急性副病毒 B19 感染近期激增的临床影响。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29903
Nabila Tabassum, Kaljit Bhuller, Amy Webster, Farah Siddiqui, Suzanna Dunkerton, Manjiri Khare, Breslin Eamonn, Hatem A. Mousa, Ian Scudamore, Damian Roland, Rachel Rowlands, Srini Bandi, Vinayak R. Rai, Atul Bagul, Jorge Jesus-Silva, Paul W. Bird, Sarah R. Young, Lucy James, Oliver T. R. Toovey, Julian W. Tang
{"title":"Clinical impact of recent surge in acute parvovirus B19 infections in Leicester UK, March–July 2024","authors":"Nabila Tabassum,&nbsp;Kaljit Bhuller,&nbsp;Amy Webster,&nbsp;Farah Siddiqui,&nbsp;Suzanna Dunkerton,&nbsp;Manjiri Khare,&nbsp;Breslin Eamonn,&nbsp;Hatem A. Mousa,&nbsp;Ian Scudamore,&nbsp;Damian Roland,&nbsp;Rachel Rowlands,&nbsp;Srini Bandi,&nbsp;Vinayak R. Rai,&nbsp;Atul Bagul,&nbsp;Jorge Jesus-Silva,&nbsp;Paul W. Bird,&nbsp;Sarah R. Young,&nbsp;Lucy James,&nbsp;Oliver T. R. Toovey,&nbsp;Julian W. Tang","doi":"10.1002/jmv.29903","DOIUrl":"10.1002/jmv.29903","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
E3 ubiquitin ligase FBXO22 inhibits SARS-CoV-2 replication via promoting proteasome-dependent degradation of NSP5 E3 泛素连接酶 FBXO22 通过促进蛋白酶体依赖性降解 NSP5 来抑制 SARS-CoV-2 的复制。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29891
Yuzheng Zhou, Wei Feng, Chuwei Yang, Xiafei Wei, Lujie Fan, Yezi Wu, Xiang Gao, Xiaotong Shen, Zheng Zhang, Juanjuan Zhao

The ubiquitin-proteasome system is frequently employed to degrade viral proteins, thereby inhibiting viral replication and pathogenicity. Through an analysis of the degradation kinetics of all the SARS-CoV-2 proteins, our study revealed rapid degradation of several proteins, particularly NSP5. Additionally, we identified FBXO22, an E3 ubiquitin ligase, as the primary regulator of NSP5 ubiquitination. Moreover, we validated the interaction between FBXO22 and NSP5, demonstrating that FBXO22-mediated ubiquitination of NSP5 facilitated its recognition by the proteasome, leading to subsequent degradation. Specifically, FBXO22 catalyzed the formation of K48-linked polyubiquitin chains on NSP5 at lysine residues 5 and 90. Knockdown of FBXO22 resulted in decreased NSP5 ubiquitination levels, increased stability, and enhanced ability to evade the host innate immune response. Notably, the protein level of FBXO22 were negatively correlated with SARS-CoV-2 load, highlighting its importance in inhibiting viral replication. This study elucidates the molecular mechanism by which FBXO22 mediates the degradation of NSP5 and underscores its critical role in limiting viral replication. The identification of FBXO22 as a regulator of NSP5 stability provides new insights and potential avenues for targeting NSP5 in antiviral strategies.

泛素-蛋白酶体系统经常被用来降解病毒蛋白,从而抑制病毒复制和致病性。通过分析所有 SARS-CoV-2 蛋白的降解动力学,我们的研究发现了一些蛋白的快速降解,尤其是 NSP5。此外,我们还发现 E3 泛素连接酶 FBXO22 是 NSP5 泛素化的主要调节因子。此外,我们还验证了 FBXO22 和 NSP5 之间的相互作用,证明 FBXO22 介导的 NSP5 泛素化促进了蛋白酶体对其的识别,从而导致随后的降解。具体来说,FBXO22 催化了 NSP5 上赖氨酸残基 5 和 90 上 K48 连接的多泛素链的形成。敲除 FBXO22 会导致 NSP5 泛素化水平降低、稳定性增加以及逃避宿主先天免疫反应的能力增强。值得注意的是,FBXO22的蛋白水平与SARS-CoV-2载量呈负相关,突出了其在抑制病毒复制中的重要性。这项研究阐明了 FBXO22 介导 NSP5 降解的分子机制,并强调了它在限制病毒复制中的关键作用。确定 FBXO22 是 NSP5 稳定性的调控因子为在抗病毒策略中靶向 NSP5 提供了新的见解和潜在途径。
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引用次数: 0
The level of expression of HPV16 early transcripts is not associated with the natural history of cervical lesions HPV16 早期转录本的表达水平与宫颈病变的自然史无关。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1002/jmv.29875
Elise Jacquin, Maëlle Saunier, Quentin Lepiller, Franck Monnien, Frédéric Mauny, Rajeev Ramanah, Xavier Carcopino, Didier Riethmuller, Christiane Mougin, Jean-Luc Prétet

The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.

宫颈癌的自然病史与高危人乳头瘤病毒(HPV)感染密切相关。人们认识到,HPV DNA 整合后,E2 开放阅读框的部分或完全缺失会阻止相应蛋白质的表达,从而导致 E6 和 E7 病毒肿瘤蛋白的上调。为了更好地描述宫颈水平的 HPV16 感染特征,我们对一系列 158 例宫颈标本进行了病毒载量、病毒 DNA 整合和病毒早期转录本表达(E2、E5 和 E6)分析,这些标本代表了宫颈疾病的全部范围。总体而言,早期转录本的检出率从 45% 到 90% 不等,并有随病变严重程度而增加的趋势。此外,高级别病变的 E2、E5 和 E6 转录本表达水平略高于无异常的宫颈标本。值得注意的是,早期转录本的表达与病毒载量明显相关,而 E2 和 E6 转录本的表达之间没有发现反相关性。早期转录本的表达与 HPV16 DNA 整合之间没有发现明显的关联,但完全整合了 HPV16 基因组的样本不携带 E2 或 E5 转录本。总之,早期 HPV16 转录本的表达似乎与病毒载量而非病变等级有关。从实际角度来看,HPV16 早期转录本的定量很难转化为宫颈癌筛查的相关生物标志物。
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引用次数: 0
Unexpected high incidence of parvovirus B19 nucleic acid detection in German blood donors in the winter/spring season 2023/2024 2023/2024 年冬春季节德国献血者中副病毒 B19 核酸检测的意外高发病率
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-08-29 DOI: 10.1002/jmv.29878
Ricarda Plümers, Jens Dreier, Cornelius Knabbe, Tanja Vollmer

In healthy adults, parvovirus B19 (PVB19) typically causes mild symptoms but can lead to severe complications in immunosuppressed individuals or those with high red blood cell turnover. Infection can occur through respiratory transmission or via transfusion, necessitating the testing of blood donations in Germany. Between 2015 and April 2024, we screened 2 105 755 blood donations for PVB19 using polymerase chain reaction. Incidence rates were calculated for three periods: pre-COVID-19 (2015–2020), during the pandemic (2020–2023), and post-COVID-19 (2023–2024). A total of 242 PVB19-positive donations were identified. In the first period, there were 101 positives out of 1 228 361 donations (incidence: 0.83/10 000). In the second period, four positives were found out of 621 222 donations (incidence: 0.06/10 000). In the third period, 137 positives were detected out of 235 088 donations (incidence: 5.35/10 000) with a striking increase of incidence between December 2023 and March 2024 (4.3–21.1/10 000 donations). Most people develop lifelong immunity after infection in childhood but the COVID-19 pandemic interventions, like masks and distancing, correlate with a decline in PVB19 infections in donors indicating an impact of hygiene measures on PVB19 infection rates.

对于健康的成年人来说,副病毒 B19 (PVB19) 通常会引起轻微的症状,但对于免疫抑制或红细胞周转率高的人来说,可能会导致严重的并发症。感染可通过呼吸道传播或输血发生,因此在德国有必要对献血进行检测。在 2015 年至 2024 年 4 月期间,我们使用聚合酶链反应对 2 105 755 份献血进行了 PVB19 筛查。我们计算了三个时期的发病率:COVID-19 之前(2015-2020 年)、大流行期间(2020-2023 年)和 COVID-19 之后(2023-2024 年)。共发现 242 例 PVB19 阳性捐献。在第一阶段,1 228 361 份捐赠中有 101 份呈阳性(发生率:0.83/10 000)。第二阶段,在 621 222 份捐献中发现了 4 份阳性捐献(发生率:0.06/10 000)。第三阶段,在 235 088 份捐赠中发现 137 例阳性(发病率:5.35/10 000),2023 年 12 月至 2024 年 3 月期间发病率显著上升(4.3-21.1/10 000 份捐赠)。大多数人在儿童时期感染后会产生终身免疫,但 COVID-19 大流行干预措施(如口罩和拉开距离)与捐献者 PVB19 感染率下降相关,表明卫生措施对 PVB19 感染率有影响。
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引用次数: 0
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Journal of Medical Virology
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