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Molecular Analysis of Coxsackievirus B2 Associated With Severe Symptoms of the Central Nervous System 与中枢神经系统严重症状相关的柯萨奇病毒 B2 分子分析。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-15 DOI: 10.1002/jmv.70066
Ilana S. Fratty, Or Kriger, Leah Weiss, Rinat Vasserman, Reut Gabai, Oran Erster, Neta S. Zuckerman, Aharona Glatman-Freedman, Yaniv Lustig, Danit Sofer, Merav Weil

Coxsackievirus B2 (CVB2) is a member of the enterovirus group known to induce a spectrum of illnesses, from mild to severe. In the summer of 2022, an unusual outbreak of enteroviral central nervous system (CNS) infections occurred that was attributed to CVB2. Cerebrospinal fluid (CSF) samples collected from patients in 2015–2022 were tested for enterovirus via RT-PCR, followed by Sanger sequencing for positive cases. CVB2 samples were further sequenced in the P1 region using NGS. A total of 30 CSF samples were identified as CVB2, with 60% of these cases occurring between June and August 2022. The 2022 CVB2 variants were associated with severe clinical symptoms, including encephalitis (50%) and ataxia (27.8%). Samples from 2015 to 2020 were also included due to the absence of these symptoms. Phylogenetic analysis revealed that CVB2 strains from 2019 to 2020 were also distinct from those obtained in 2022. Amino acid analysis of the capsid proteins VP1, VP2, and VP3 identified three unique substitutions with potential antigenic significance in the 2022 variant: S67A in VP2, and T93A and E274D in VP1. These substitutions were not present in earlier strains or reported in the literature, suggesting they may influence the virus's virulence. The clinical observations from this study highlight new patterns of CVB2 infection in the CNS that had not been previously observed. Additionally, it identifies unique genetic changes in the 2022 CVB2 variant that may account for the increased virulence seen in the 2022 outbreak. However, further analysis is required to validate this assumption.

柯萨奇病毒 B2(CVB2)是肠道病毒中的一种,可诱发从轻微到严重的各种疾病。2022 年夏天,爆发了一次不寻常的肠道病毒中枢神经系统(CNS)感染,其病因就是 CVB2。通过 RT-PCR 对 2015-2022 年收集的患者脑脊液(CSF)样本进行了肠道病毒检测,随后对阳性病例进行了 Sanger 测序。使用 NGS 对 CVB2 样本的 P1 区进行了进一步测序。共有 30 份 CSF 样本被鉴定为 CVB2,其中 60% 的病例发生在 2022 年 6 月至 8 月期间。2022 年的 CVB2 变异与严重的临床症状有关,包括脑炎(50%)和共济失调(27.8%)。由于没有出现这些症状,2015年至2020年的样本也被包括在内。系统发育分析表明,2019年至2020年的CVB2菌株也有别于2022年获得的菌株。对囊膜蛋白 VP1、VP2 和 VP3 的氨基酸分析发现,在 2022 年的变异株中,有三个具有潜在抗原意义的独特取代:VP2 中的 S67A 以及 VP1 中的 T93A 和 E274D。这些置换在早期毒株中并不存在,文献中也未见报道,这表明它们可能会影响病毒的毒力。这项研究的临床观察结果突显了 CVB2 在中枢神经系统感染的新模式,这是以前从未观察到的。此外,该研究还发现了 2022 年 CVB2 变体中独特的基因变化,这可能是 2022 年疫情中病毒毒力增强的原因。然而,要验证这一假设还需要进一步的分析。
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引用次数: 0
Rhinovirus in pediatric respiratory infections: More than a simple cold 小儿呼吸道感染中的鼻病毒:不仅仅是简单的感冒
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-15 DOI: 10.1002/jmv.29959
Antonietta Giannattasio, Marco Maglione, Marco Sarno, Chiara Botti, Ornella Leone, Marcella Contieri, Agnese Sara Ciccarelli, Camilla Calì, Fabio Savoia, Vincenzo Tipo
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引用次数: 0
Concerns on a New Varicella Vaccine Introduced in Korea 对韩国引进的新型水痘疫苗的担忧。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-15 DOI: 10.1002/jmv.70069
Joowon Lee
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引用次数: 0
Long-Term Infection With a Particular Human Papillomavirus (HPV) Genotype, HPV Subtype, or HPV Genomic Variant Does not Significantly Influence the Clinical Course of Recurrent Respiratory Papillomatosis 长期感染特定人类乳头状瘤病毒 (HPV) 基因型、HPV 亚型或 HPV 基因组变异不会显著影响复发性呼吸道乳头状瘤病的临床病程。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.70060
Daša Gluvajić, Lea Hošnjak, Tomaž Mark Zorec, Nina Gale, Irena Hočevar Boltežar, Mario Poljak

Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPV) 6 and 11, but the role of their genomic variants in the disease's clinical course is unclear. This study investigated whether long-term persistence of a particular HPV genotype, subtype or genomic variant influences the RRP clinical course. HPV genotyping was performed in paired baseline and follow-up RRP laryngeal tissue specimens of 59 patients. HPV6 and HPV11 genomic variants were determined in paired tissue specimens taken at least 10 years apart in 20 selected patients. HPV was identified in 58/59 patients, most commonly HPV6 (40/58), followed by HPV11 (17/58). The most prevalent HPV genomic variant was HPV11 A2. HPV6 A and HPV6 B1 were most frequent in aggressive RRP. In all patients, identical HPV genomic variants were identified in both paired specimens. RRP results from a long-term infection with the same HPV genomic variant that can be identified decades after disease onset. We report the longest duration of genetically confirmed persistent HPV infection in peer-reviewed literature, during a 44-year interval in a patient with HPB6 B1. This study suggests that infection with a particular HPV genotype, subtype, or genomic variant does not significantly influence the clinical course of RRP.

复发性呼吸道乳头状瘤病(RRP)是由人类乳头状瘤病毒(HPV)6和11引起的,但其基因组变异在该病临床过程中的作用尚不清楚。本研究调查了特定 HPV 基因型、亚型或基因组变体的长期存在是否会影响 RRP 的临床病程。对59名患者的配对基线和随访RRP喉组织标本进行了HPV基因分型。对 20 名选定患者中至少相隔 10 年的配对组织标本进行了 HPV6 和 HPV11 基因组变异测定。在 58/59 例患者中发现了 HPV,其中最常见的是 HPV6(40/58),其次是 HPV11(17/58)。最常见的 HPV 基因组变体是 HPV11 A2。在侵袭性 RRP 中,HPV6 A 和 HPV6 B1 最为常见。在所有患者的两份配对标本中都发现了相同的 HPV 基因组变异。RRP是由于长期感染相同的HPV基因组变体所致,这种变体可在发病数十年后才被发现。我们报告了在同行评议的文献中,一名 HPB6 B1 患者在 44 年间持续感染 HPV 的最长时间。这项研究表明,感染特定的 HPV 基因型、亚型或基因组变异不会对 RRP 的临床病程产生重大影响。
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引用次数: 0
Simple, direct amplification of RNA-containing paper discs for diagnosing the hepatitis C virus 用于诊断丙型肝炎病毒的含 RNA 纸片的简单直接扩增。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.29919
Daehyun Chu, Yoon-Hee Oh, Heungsup Sung, Dae-Hyun Ko, Heung-Bum Oh, Sang-Hyun Hwang

Nucleic acid extraction (NAE) is crucial for molecular diagnostics but presents challenges in point-of-care testing (POCT) and decentralized settings. We developed a streamlined, paper-based NAE method for hepatitis C virus (HCV) RNA amplification, suitable for integration into POCT and lab-on-a-chip systems. This method uses Fusion 5 paper discs, completing extraction in under 30 min without centrifugation. The nucleic acids on the disc can be directly used or eluted for amplification. We validated this method's compatibility with reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR (RQ-PCR), and loop-mediated isothermal amplification (LAMP), demonstrating versatility across amplification platforms. Clinical evaluation (n = 60) showed 100% sensitivity and specificity with a low detection limit of ~101 IU/mL. Results matched those from standard HCV RQ-PCR, confirming accuracy. Additionally, incorporating polyethylene glycol (PEG) improves extraction efficiency, eliminating the need for ethanol treatment and washing/drying steps. This modification enhances performance and suitability for field applications. Our paper-based HCV amplification is affordable and user-friendly, making it valuable for decentralized HCV detection and supporting global health initiatives.

核酸提取(NAE)对分子诊断至关重要,但在床旁检测(POCT)和分散环境中却面临挑战。我们开发了一种简化的、基于纸张的丙型肝炎病毒(HCV)RNA 扩增 NAE 方法,适合集成到 POCT 和芯片实验室系统中。该方法使用 Fusion 5 纸片,可在 30 分钟内完成提取,无需离心。纸片上的核酸可直接使用或洗脱用于扩增。我们验证了这种方法与反转录聚合酶链反应(RT-PCR)、实时定量 PCR(RQ-PCR)和环介导等温扩增(LAMP)的兼容性,证明了它在各种扩增平台上的通用性。临床评估(n = 60)显示灵敏度和特异性均为 100%,检测限低至约 101 IU/mL。结果与标准 HCV RQ-PCR 的结果一致,证实了其准确性。此外,加入聚乙二醇(PEG)可提高提取效率,省去乙醇处理和洗涤/干燥步骤。这种改良提高了性能和现场应用的适用性。我们的纸基 HCV 扩增技术经济实惠、操作简便,对分散式 HCV 检测和支持全球健康计划非常有价值。
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引用次数: 0
The Distribution of HR-HPV E6/E7 DNA and mRNA by Histological Grade and the Clinical Performance for Detection of Cervical Cancer and Precancer 按组织学分级划分的 HR-HPV E6/E7 DNA 和 mRNA 分布情况以及检测宫颈癌和癌前病变的临床表现。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.70026
Ruoji Pi, Tingyuan Li, Hua Zhang, Hang Zhou, Yuan Yang, Yu Dai, Zeni Wu, Mingyue Jiang, Wen Chen, Lan Zhu

High-risk human papillomavirus (HR-HPV) testing, utilizing both DNA and RNA methods, offers enhanced sensitivity compared to cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). Meanwhile, HR-HPV E6 and E7 mRNAs are more likely to differentiate the transient infection from the persistent than DNA. Aptima HPV can not only detect HPV mRNA but also HPV DNA though it is much more efficient at detecting HPV RNA than DNA. Currently, there are few studies on the distribution of HPV E6 and E7 mRNA and DNA in the same individual. It is interesting to compare the clinical performance of the Onclarity and Aptima HPV assays and to assess variations in viral load across different histological grades at both DNA and mRNA levels. The analysis included 1607 women (902 from a cervical cancer screening population and 705 inpatients and outpatients), with cervical cytological samples tested using the Aptima and Onclarity HPV assays. Both assays demonstrated high agreement for HPV types 18/45 and 16. Signal-to-cutoff (S/CO) values and Ct values for various HR-HPV types increased with histological severity from normal tissue to cancer. Notably, HPV18 Ct values exceeded those for HPV16 and 45 in women with ≥ CIN1 lesions but decreased sharply in cancer cases. Across the screening population, both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions. The area under the curve (AUC) for CIN2+ and CIN3+ detection in the study population was robust (CIN2+: 0.880, 0.863; CIN3+: 0.881, 0.863). The DNA level for various HR-HPV types increased with histological severity from normal tissue to cancer, which might impact the performance of Aptima HPV assay. Both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions.

高危人乳头瘤病毒(HR-HPV)检测采用 DNA 和 RNA 两种方法,与细胞学相比,检测高级别宫颈上皮内瘤变(CIN2+)的灵敏度更高。同时,HR-HPV E6 和 E7 mRNA 比 DNA 更能区分一过性感染和持续性感染。Aptima HPV 不仅能检测 HPV mRNA,还能检测 HPV DNA,但其检测 HPV RNA 的效率比检测 DNA 高得多。目前,关于 HPV E6 和 E7 mRNA 和 DNA 在同一人体内分布的研究很少。比较 Onclarity 和 Aptima HPV 检测试剂盒的临床性能,并评估不同组织学分级在 DNA 和 mRNA 水平上的病毒载量变化是很有意义的。分析对象包括1607名妇女(902名来自宫颈癌筛查人群,705名住院和门诊患者),宫颈细胞学样本使用Aptima和Onclarity HPV检测法进行检测。两种检测方法对 18/45 型和 16 型 HPV 的检测结果显示出很高的一致性。各种HR-HPV类型的信噪比(S/CO)值和Ct值随着组织学严重程度(从正常组织到癌症)的增加而增加。值得注意的是,在≥CIN1 病变的妇女中,HPV18 的 Ct 值超过了 HPV16 和 45,但在癌症病例中则急剧下降。在整个筛查人群中,这两种检测方法在检测 CIN2+ 病变方面显示出相似的灵敏度和预测值。在研究人群中,检测 CIN2+ 和 CIN3+ 的曲线下面积(AUC)很高(CIN2+:0.880,0.863;CIN3+:0.881,0.863)。从正常组织到癌症,各种HR-HPV类型的DNA水平随着组织学严重程度的增加而增加,这可能会影响Aptima HPV检测的性能。两种检测方法在检测 CIN2+ 病变方面的灵敏度和预测值相似。
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引用次数: 0
Epidemiological Characteristics of Neuro-Specific Antibodies Following Viral Infections 病毒感染后神经特异性抗体的流行病学特征
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.70050
Yang Su, Jierui Wang, Yan Ren, Songtao Xu, Yanjun Si, Meng Tang, Yi Li, Minjin Wang

This study aims to explore the epidemiological characteristics of neuro-specific antibodies (ns-Ab) induced by different viral infections within the central nervous system (CNS). Additionally, it seeks to compare the autoimmune effects following several typical viral infections in CNS. We conduct a retrospective study to compare and analyze the prevalence trends of ns-Ab in patients with different viral infections. Additionally, evaluate the intensity of CNS inflammatory responses postviral infection by correlating clinical characteristics and laboratory findings, and briefly demonstrate the immune effects in CNS following various viral infections. This study retrospectively collected data from 1037 patients hospitalized with suspected CNS infections. A total of 654 patients (63.1%) were included in the final analysis. A higher proportion of patients with pathogens present in their cerebrospinal fluid (CSF) (114 out of 332, 34.3%) tested positive for ns-Ab compared to those without pathogens (70 out of 322, 21.7%) (p = 0.0004). Specifically, the screening rate for ns-Ab in patients with CNS viral infections (83 out of 165, 50.3%) and the prevalence of ns-Ab (27 out of 83, 32.5%) were significantly higher than in those with other pathogen infections (p < 0.0001 and p = 0.016, respectively). Among these, human herpesvirus 7 (HHV7) patients had the highest detection rate of ns-Ab during the disease course (11 out of 26, 42.3%), but exhibited infection characteristics distinctly different from those of herpes simplex virus 1 (HSV1). Viral infections significantly promote the development of autoimmune responses in CNS. The production of ns-Ab and the subsequent autoimmune response vary across different viral infections. There is a strong statistical correlation between HHV7 and the presence of ns-Ab, suggesting that HHV7 may serve as an early indicator of secondary autoimmune response following CNS infections.

本研究旨在探讨中枢神经系统(CNS)内不同病毒感染诱导的神经特异性抗体(ns-Ab)的流行病学特征。此外,本研究还试图比较中枢神经系统中几种典型病毒感染后的自身免疫效应。我们进行了一项回顾性研究,以比较和分析不同病毒感染患者中 ns-Ab 的流行趋势。此外,通过临床特征和实验室检查结果的相关性评估中枢神经系统感染后炎症反应的强度,并简要说明各种病毒感染后中枢神经系统的免疫效应。本研究回顾性收集了 1037 名疑似中枢神经系统感染住院患者的数据。共有 654 名患者(63.1%)被纳入最终分析。与没有病原体的患者(322 人中有 70 人,占 21.7%)相比,脑脊液(CSF)中存在病原体的患者(332 人中有 114 人,占 34.3%)ns-Ab 检测呈阳性的比例更高(p = 0.0004)。具体而言,中枢神经系统病毒感染患者的 ns-Ab 筛查率(165 人中有 83 人,占 50.3%)和 ns-Ab 患病率(83 人中有 27 人,占 32.5%)明显高于其他病原体感染患者(p=0.0004)。
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引用次数: 0
Impact of COVID-19 on the Prevalence and Drug Resistance of Bacteria Isolated From Bacterial Meningitis Cerebrospinal Fluid in Shandong Province: A Multicenter Retrospective Study COVID-19 对山东省细菌性脑膜炎脑脊液分离细菌流行率和耐药性的影响:一项多中心回顾性研究。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.70063
Chunyan Zhang, Mengyuan Wang, Shuhong Sun, Maoli Yi, Shifu Wang

Our objective was to evaluate the ramifications of the 2019 coronavirus disease (COVID-19) pandemic on the microbial profile and antimicrobial resistance patterns of bacteria isolated from cerebrospinal fluid (CSF) specimens of patients with bacterial meningitis. We conducted a retrospective analysis of laboratory results and clinical records about positive CSF cultures reported by the SPARSS network from 2017 to 2023. The study covered three distinct periods: January 2017 to December 2019 (before the COVID-19 pandemic), January 2020 to December 2022 (during the COVID-19 pandemic), and January 2023 to December 2023 (after the COVID-19 pandemic), with a total of 5793 CSF isolates collected. Notably, the proportion of male patients (61.3%) was higher than that of females. After COVID-19, we observed a notable shift in the seasonal peak of CSF pathogens, with a delay of approximately 3 months. Remarkable alterations were evident in both pediatric and adult CSF isolate profiles. In children, the predominant pathogens included coagulase-negative Staphylococcus (CoNS), Streptococcus pneumonia, and Escherichia coli. Notably. After COVID-19, there was a significant decrease in the proportion of CoNS (p = 0.0039) and a notable increase in E. coli (p = 0.0067). In adults, the top three pathogens were CoNS, Acinetobacter baumannii, and Klebsiella pneumoniae. After the pandemic, we observed a significant reduction in the prevalence of A. baumannii (p = 0.0059), while the proportions of K. pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis increased significantly (p < 0.05). Additionally, among multidrug-resistant bacteria, the detection rate of carbapenem-resistant E. coli escalated (p = 0.0375). Antimicrobial susceptibility analysis indicated a declining trend in resistance rates for CoNS and A. baumannii to certain antibiotics following the pandemic. Conversely, resistance to imipenem in A. baumannii increased. In conclusion, the COVID-19 pandemic has significantly influenced the composition, antimicrobial resistance patterns, and epidemiological dynamics of CSF-isolated bacteria in Shandong province. To effectively address these changes, ongoing and dynamic surveillance of pathogen trends and antimicrobial resistance rate is essential.

我们的目的是评估 2019 年冠状病毒病(COVID-19)大流行对从细菌性脑膜炎患者脑脊液(CSF)标本中分离出的细菌的微生物特征和抗菌药耐药性模式的影响。我们对 SPARSS 网络报告的 2017 年至 2023 年 CSF 培养阳性的实验室结果和临床记录进行了回顾性分析。研究涵盖了三个不同时期:2017年1月至2019年12月(COVID-19大流行之前)、2020年1月至2022年12月(COVID-19大流行期间)和2023年1月至2023年12月(COVID-19大流行之后),共收集到5793份CSF分离物。值得注意的是,男性患者的比例(61.3%)高于女性。COVID-19 之后,我们观察到 CSF 病原体的季节性高峰发生了明显变化,延迟了约 3 个月。儿童和成人的脑脊液分离物特征都发生了显著变化。在儿童中,主要病原体包括凝固酶阴性葡萄球菌(CoNS)、肺炎链球菌和大肠埃希菌。值得注意的是在 COVID-19 之后,CoNS 的比例明显下降(p = 0.0039),而大肠杆菌的比例明显上升(p = 0.0067)。在成人中,前三位病原体分别是柯萨奇杆菌、鲍曼不动杆菌和肺炎克雷伯菌。大流行后,我们观察到鲍曼不动杆菌的流行率显著下降(p = 0.0059),而肺炎克雷伯菌、铜绿假单胞菌、泄殖腔肠杆菌和粪肠球菌的比例显著上升(p = 0.0067)。
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引用次数: 0
Norovirus Genotypes Circulating in NHS Greater Glasgow and Clyde, Scotland, During Winter 2023/2024 2023/2024 年冬季苏格兰 NHS 大格拉斯哥和克莱德地区流行的诺罗病毒基因型。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.70061
Rachael M. Tomb, Alasdair R. Maclean, Rory N. Gunson
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引用次数: 0
The Antigen-Specific Response of NK Cells to SARS-CoV-2 Correlates With KIR2DS4 Expression NK细胞对SARS-CoV-2的抗原特异性反应与KIR2DS4表达有关
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-11-14 DOI: 10.1002/jmv.70057
M. O. Ustiuzhanina, A. A. Boyko, J. D. Vavilova, A. E. Siniavin, M. A. Streltsova, I. V. Astrakhantseva, M. S. Drutskaya, D. M. Chudakov, E. I. Kovalenko

Natural killer (NK) cells play a pivotal role in the immune response against viral infections, including SARS-CoV-2. However, our understanding of memory NK cell responses in the context of SARS-CoV-2 remains limited. To address this, we investigated the memory-like response of NK cells to SARS-CoV-2 peptides, presented by autologous cells. Blood samples from 45 donors underwent analysis for SARS-CoV-2 IgG antibodies, categorizing them into four groups based on the antibody kind and level. NK cells from SARS-CoV-2-experienced donors demonstrated enhanced degranulation and activation levels, IFNγ production and proliferative potential in response to SARS-CoV-2 peptides. Investigation of highly proliferating NK cells demonstrated the formation of distinct clusters depending on the SARS-CoV-2 peptide supplementation and the donor group. RNA sequencing revealed differential gene expression patterns, highlighting metabolism, protein transport, and immune response genes. Notably, KIR2DS4 expression correlated with enhanced IFNγ production, degranulation and proliferation levels, suggesting a role in SARS-CoV-2 recognition. Collectively, these findings provide detailed insights into antigen-specific NK cell responses to SARS-CoV-2 peptides, indicating potential mechanisms underlying NK cell activation in antiviral immunity.

自然杀伤(NK)细胞在抗病毒感染(包括 SARS-CoV-2)的免疫反应中发挥着关键作用。然而,我们对记忆性 NK 细胞对 SARS-CoV-2 的反应的了解仍然有限。为了解决这个问题,我们研究了 NK 细胞对自体细胞呈现的 SARS-CoV-2 多肽的记忆反应。我们对 45 名献血者的血样进行了 SARS-CoV-2 IgG 抗体分析,并根据抗体种类和水平将其分为四组。有 SARS-CoV-2 经验的供体的 NK 细胞对 SARS-CoV-2 多肽的脱颗粒和活化水平、IFNγ 的产生和增殖潜力都有所提高。对高度增殖的 NK 细胞进行的调查显示,根据 SARS-CoV-2 多肽的补充情况和供体组别,形成了不同的集群。RNA 测序显示了不同的基因表达模式,突出了新陈代谢、蛋白质转运和免疫反应基因。值得注意的是,KIR2DS4的表达与IFNγ的产生、脱颗粒和增殖水平的增强相关,表明其在SARS-CoV-2识别中的作用。总之,这些发现详细揭示了抗原特异性 NK 细胞对 SARS-CoV-2 多肽的反应,表明了 NK 细胞激活抗病毒免疫的潜在机制。
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引用次数: 0
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Journal of Medical Virology
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