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Prevalence and Genetic Diversity of Respiratory Syncytial Virus Reinfections in Young Thai Children, 2016–2023 2016-2023年泰国儿童呼吸道合胞病毒再感染的患病率和遗传多样性
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-18 DOI: 10.1002/jmv.70132
Siripat Pasittungkul, Ilada Thongpan, Preeyaporn Vichaiwattana, Watchaporn Chuchaona, Sarawut Khongwichit, Nasamon Wanlapakorn, Sompong Vongpunsawad, Yong Poovorawan

Although a vaccine for respiratory syncytial virus (RSV) is now available for pregnant women and the elderly, RSV remains a significant cause of respiratory illness in children globally. Reinfections by the same or different RSV subgroups in children residing in the tropics are currently under-studied. Therefore, we examined the patterns of RSV infection and reinfection in Thai children aged ≤ 5 years with respiratory symptoms from 2016 to 2023. Screening of 7710 pediatric respiratory specimens identified 1245 RSV-positive samples (16.1%), mostly from the rainy months (July–November). Interestingly, 74 children experienced two infections, and 6 had three infections. Reinfection by different RSV subgroups occurred in 30 children: 21 were initially infected with RSV-B and later with RSV-A, while 9 had the reverse pattern. Reinfections only by either RSV-A or RSV-B were observed in 22 and 2 children, respectively, with one child infected with RSV-A three times. All RSV-A reinfections belonged to the ON1 genotype, while RSV-B reinfections were BA9. Notably, reinfections across different seasons were observed within homologous pairs. These findings suggest a transitory immunity to natural RSV infection and provide the knowledge that may help optimize pediatric vaccination schedule. Ongoing epidemiological data on RSV are essential in monitoring genotype circulation and vaccine effectiveness.

虽然现在有针对孕妇和老年人的呼吸道合胞病毒(RSV)疫苗,但RSV仍然是全球儿童呼吸道疾病的一个重要原因。居住在热带地区的儿童中由相同或不同的呼吸道合胞病毒亚群再感染的情况目前尚在研究中。因此,我们研究了2016年至2023年泰国≤5岁有呼吸道症状儿童RSV感染和再感染的模式。对7710份儿童呼吸道标本进行筛查,发现1245份rsv阳性样本(16.1%),主要来自雨季(7 - 11月)。有趣的是,74名儿童有两次感染,6名有三次感染。30名儿童发生不同RSV亚群再感染:21名儿童最初感染RSV- b,后来感染RSV- a, 9名儿童感染RSV- a。22例患儿仅感染RSV-A型,2例患儿仅感染RSV-B型,其中1例患儿三次感染RSV-A型。RSV-A再感染均为ON1基因型,RSV-B再感染均为BA9基因型。值得注意的是,在同源对中观察到不同季节的再感染。这些发现提示了对自然呼吸道合胞病毒感染的短暂免疫,并提供了可能有助于优化儿科疫苗接种计划的知识。关于RSV的持续流行病学数据对于监测基因型循环和疫苗有效性至关重要。
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引用次数: 0
Genome-Wide Association Study of Persistent Anal Human Papillomavirus Infection Among HIV-Positive Males in Taizhou, China: A Cohort Study 中国台州 HIV 阳性男性持续性肛门人类乳头瘤病毒感染的全基因组关联研究:一项队列研究。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-17 DOI: 10.1002/jmv.70126
Jing Zhang, Shuang Shao, Xiaoxiao Chen, Shanling Wang, Weiwei Shen, Yali Xie, Zhen Zhang, Yajun Lin, Zhebin Lin, Yan Li, Yingying Ding, Na He, Haijiang Lin, Xing Liu

The determinants of persistent human papillomavirus (HPV) infection remain largely unknown, and existing studies have predominantly focused on the female population. Individual genetic background may influence the persistence of HPV infection, we the evidence overall and among human immunodeficiency virus (HIV)-positive males are very limited. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with anal HPV persistence, based on a cohort designed to study the natural history of anal HPV infection among HIV-positive males in Taizhou, China from 2016 to 2022. A total of 322 HIV-positive males with anal HPV infection, with a mean age of 43.0 (standard deviation [SD]: 13.8) years, were included in this GWAS. The median follow-up time was 1.8 (interquartile range [IQR]: 1.5–2.0) years. The persistence of any type of HPV infection was 53.4%. After adjusting for age and sexual orientation, there were 2 SNPs with p < 1 × 10−5 and 24 SNPs with p < 1 × 10−4. The most closely associated with HPV persistence in additive models were rs7359031 (LOC105370461, odds ratio [OR]T/C = 0.36, 95% confidence interval [CI]: 0.24–0.56; p = 6.67 × 10−6) located at 14q21.1, and rs11046048 (PYROXD1, ORC/A = 0.41, 95% CI: 0.28–0.60; p = 7.80 × 10−6) located at 12p12.1. Other SNPs were mainly located at 6q23.3 (HBS1L-MYB) and 6p21.33 (CCHCR1, PSORS1C3). LOC105370461, PYROXD1, HBS1L-MYB, CCHCR1, and PSORS1C3 may be susceptible genes for HPV persistence. We appeal further studies to validate these associations and examine the underlying mechanisms.

持续的人乳头瘤病毒(HPV)感染的决定因素在很大程度上仍然未知,现有的研究主要集中在女性人群。个体遗传背景可能影响HPV感染的持续性,但总体证据和人类免疫缺陷病毒(HIV)阳性男性的证据非常有限。我们开展了一项全基因组关联研究(GWAS),以确定与肛门HPV持续存在相关的单核苷酸多态性(snp),该研究基于一项旨在研究2016年至2022年中国台州hiv阳性男性肛门HPV感染自然史的队列研究。共纳入322例hiv阳性男性肛门HPV感染,平均年龄为43.0岁(标准差[SD]: 13.8)岁。中位随访时间为1.8年(四分位数间距[IQR]: 1.5-2.0)。任何类型HPV感染的持续性为53.4%。在调整年龄和性取向后,p -5 snp有2个,p -4 snp有24个。在加性模型中与HPV持久性最密切相关的是rs7359031 (LOC105370461),比值比[OR]T/C = 0.36, 95%可信区间[CI]: 0.24-0.56;p = 6.67 × 10-6)位于14q21.1, rs11046048 (PYROXD1, ORC/A = 0.41, 95% CI: 0.28-0.60;P = 7.80 × 10-6)位于12p12.1。其他snp主要位于6q23.3 (HBS1L-MYB)和6p21.33 (CCHCR1, PSORS1C3)。LOC105370461、PYROXD1、HBS1L-MYB、CCHCR1和PSORS1C3可能是HPV持久性的易感基因。我们呼吁进一步的研究来验证这些关联,并检查潜在的机制。
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引用次数: 0
Temporal Dynamics and (Para)Clinical Factors Associated With (Long) Viral RNA Shedding in COVID-19 Nonhospitalized Individuals – The COVID-HOME Study 与COVID-19非住院个体(长)病毒RNA脱落相关的时间动态和(Para)临床因素- COVID-HOME研究
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-17 DOI: 10.1002/jmv.70125
Larissa E. Vlaming-van Eijk, Imran A. Ertugrul, Vinit Upasani, Karin I. Wold, María F. Vincenti-Gonzalez, Alida C. M. Veloo, Arno R. Bourgonje, Daniele Pantano, Lilli Gard, Gerolf de Boer, Hubert G. M. Niesters, Alexander W. Friedrich, Marjolein Knoester, Bernardina T. F. van der Gun, Izabela A. Rodenhuis-Zybert, Adriana Tami

Understanding temporal patterns and determinants of RNA shedding is important to comprehend SARS-CoV-2 transmission and improve biosafety/isolation guidelines. Nonhospitalized SARS-CoV-2-infected individuals and household members were enrolled between March 2020 and June 2021 and followed prospectively ≥ 3 weeks during acute disease and at 3-, 6-, 12-, and 18-months to obtain (para)clinical data and biospecimens. Flow cytometry-based surrogate assay (FlowSA) detected viable SARS-CoV-2. Determinants of long RNA shedding ( ≥ 21 days) were investigated. RNA shedding median duration was 14 days (IQR 8.0–21.0) for nasopharyngeal/throat (NPT) and 7 days (IQR 1.0–27.0) for feces— but 20 days (IQR 7.0–27.8) when excluding individuals positive at a single timepoint (25.2%). Among 17 NPT long shedders with FlowSA results, 12 (70.6%) demonstrated viable virus. NPT long shedding was independently positively associated with endocrine disease and chills. Fecal long shedding was independently inversely associated with age, female sex, and fatigue, but positively with vomiting. No associations with long-term COVID-19-related complaints were observed. Finally, fecal long shedders demonstrated higher anti-spike(S1) IgG levels over 18-month follow-up than non-long shedders (p = 0.006). (Long) SARS-CoV-2 RNA shedding in NPT and feces associates with age and acute—but not prolonged—symptoms. The roles of prolonged infectious shedding and fecal shedding in transmission and immunity remain unclear.

了解RNA脱落的时间模式和决定因素对于理解SARS-CoV-2传播和改进生物安全/分离指南非常重要。非住院的sars - cov -2感染者和家庭成员在2020年3月至2021年6月期间入组,并在急性疾病期间和3、6、12和18个月期间前瞻性随访≥3周,以获得(para)临床数据和生物标本。基于流式细胞术的替代检测(FlowSA)检测到活的SARS-CoV-2。研究长时间RNA脱落(≥21天)的决定因素。鼻咽/咽喉(NPT)中位RNA脱落持续时间为14天(IQR 8.0-21.0),粪便中位RNA脱落持续时间为7天(IQR 1.0-27.0),但排除单个时间点阳性个体(25.2%)时,RNA脱落持续时间为20天(IQR 7.0-27.8)。在17个具有FlowSA结果的NPT长脱壳中,12个(70.6%)显示病毒存活。NPT长脱落与内分泌疾病和寒战独立正相关。粪便长脱落与年龄、女性和疲劳独立负相关,但与呕吐正相关。未观察到与covid -19相关的长期投诉有关联。最后,在18个月的随访中,粪便长脱落者比非长脱落者表现出更高的抗穗状抗体(S1) IgG水平(p = 0.006)。(长)NPT和粪便中的SARS-CoV-2 RNA脱落与年龄和急性(但不长期)症状有关。长时间的感染脱落和粪便脱落在传播和免疫中的作用尚不清楚。
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引用次数: 0
Epstein-Barr Virus Infection Presenting With Acute Gastrointestinal Involvement. Report of Two Cases of Epstein-Barr Virus Colitis in Kidney-Transplant Recipients and Scoping Review of the Literature 表现为急性胃肠道受累的 Epstein-Barr 病毒感染。两例肾移植受者Epstein-Barr病毒性结肠炎病例报告及文献综述。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-17 DOI: 10.1002/jmv.70121
Alejandro Díez-Vidal, Carlos Arroyo-Acosta, Carolina Elvira-Lafuente, Beatriz Díaz-Pollán, David Grandioso-Vas, Belén Loeches, Javier Azores-Moreno, Cristina Marcelo-Calvo, Patricia Martínez-Martín, María Elena González-García

Epstein-Barr virus (EBV) is a herpesvirus capable of establishing lifelong latent infections, leading to a wide spectrum of diseases. It can affect multiple organs, including the gastrointestinal tract, typically through lymphoproliferative syndromes or gastric cancer, while acute gastrointestinal disease is rare and poorly understood. Two cases of EBV-induced acute colitis in kidney transplant recipients were described. Additionally, a scoping review of the literature was conducted to identify all reported cases of EBV infection presenting with acute gastrointestinal involvement. A total of 11 174 articles from PubMed and Embase were analyzed, from which 30 articles were ultimately selected, encompassing 33 cases. Two distinct patient profiles emerged. Patients with gastric-limited disease were typically healthy women and exhibited a benign course, characterized by a more acute presentation and complete recovery in all cases. In contrast, patients with intestinal disease were often immunocompromised, presenting with deep colonic ulcers frequently associated with rectal bleeding, high rates of perforation, frequent need for surgical intervention, and significant mortality. Antiviral therapy and reduction of immunosuppression were commonly employed, although no specific treatment approach demonstrated a clear benefit in reducing mortality or complications. In conclusion, EBV-related gastrointestinal disease varies by patient immunocompetence and the site of involvement. Gastric-limited disease usually has a favorable prognosis, while intestinal involvement in immunocompromised patients is linked to severe complications and higher mortality. Individualized treatment strategies and vigilant long-term follow-up are needed due to the lack of standardized treatment protocols and the risk of relapse or development of EBV-associated lymphoproliferative disorders.

eb病毒(EBV)是一种疱疹病毒,能够建立终身潜伏感染,导致广泛的疾病。它可以影响多个器官,包括胃肠道,通常通过淋巴增生性综合征或胃癌,而急性胃肠道疾病是罕见的,知之甚少。本文报道了肾移植受者中2例eb病毒引起的急性结肠炎。此外,对文献进行了范围审查,以确定所有报告的EBV感染病例,表现为急性胃肠道受累。共分析了PubMed和Embase中的11 174篇文章,最终从中选择了30篇文章,包含33例病例。出现了两种不同的患者概况。胃局限性疾病的患者通常是健康女性,表现为良性病程,其特点是症状更急性,所有病例均完全康复。相比之下,肠道疾病患者往往免疫功能低下,表现为深结肠溃疡,常伴有直肠出血,穿孔率高,经常需要手术干预,死亡率高。通常采用抗病毒治疗和减少免疫抑制,尽管没有特定的治疗方法在降低死亡率或并发症方面显示出明显的益处。总之,ebv相关的胃肠道疾病因患者的免疫能力和受累部位而异。胃局限性疾病通常有良好的预后,而免疫功能低下患者的肠道受累与严重并发症和更高的死亡率有关。由于缺乏标准化的治疗方案和eb病毒相关淋巴增生性疾病复发或发展的风险,需要个性化的治疗策略和警惕的长期随访。
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引用次数: 0
RNA Helicase DDX5 in Association With IFI16 and the Polycomb Repressive Complex 2 Silences Transcription of the Hepatitis B Virus by Interferon RNA 螺旋酶 DDX5 与 IFI16 和多聚核酸抑制复合体 2 结合,通过干扰素抑制乙型肝炎病毒的转录
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-16 DOI: 10.1002/jmv.70118
Zhili Li, Naimur Rahman, Cheng Bi, Rodrigo Mohallem, Aryamav Pattnaik, Majid Kazemian, Fang Huang, Uma K. Aryal, Ourania Andrisani

RNA helicase DDX5 is a host restriction factor for hepatitis B virus (HBV) biosynthesis. Mass spectrometry (LC-MS/MS) identified significant DDX5-interacting partners, including interferon-inducible protein 16 (IFI16) and RBBP4/7, an auxiliary subunit of polycomb repressive complex 2 (PRC2). DDX5 co-eluted with IFI16, RBBP4/7, and core PRC2 subunits in size exclusion chromatography fractions derived from native nuclear extracts. Native gel electrophoresis of DDX5 immunoprecipitants revealed a 750 kDa DDX5/IFI16/PRC2 complex, validated by nanoscale co-localization via super-resolution microscopy. Prior studies demonstrated that IFI16 suppresses HBV transcription by binding to the interferon-sensitive response element of covalently closed circular DNA (cccDNA), reducing H3 acetylation and increasing H3K27me3 levels by an unknown mechanism. Herein, we demonstrate that ectopic expression of IFI16 inhibited HBV transcription from recombinant rcccDNA, correlating with increased IFI16 binding to rcccDNA, reduced H3 acetylation, and elevated H3K27me3, determined by chromatin immunoprecipitation. Importantly, the inhibitory effect of ectopic IFI16 on HBV transcription was reversed by siRNA-mediated knockdown of DDX5 and EZH2, the methyltransferase subunit of PRC2. This reversal was associated with decreased IFI16 binding to rcccDNA, enhanced H3 acetylation, and reduced H3K27me3. Similarly, endogenous IFI16 induced by interferon-α inhibited HBV rcccDNA transcription in a DDX5- and PRC2-dependent manner. In HBV-infected HepG2-NTCP cells, the antiviral effect of interferon-α was abrogated upon knockdown of DDX5 and EZH2, underscoring the crucial role of the DDX5 complex in IFI16-mediated antiviral response. In conclusion, in response to interferon, DDX5 partners with IFI16 to bind cccDNA, directing PRC2 to epigenetically silence cccDNA chromatin, thereby regulating immune signaling and HBV transcription.

RNA 螺旋酶 DDX5 是乙型肝炎病毒(HBV)生物合成的宿主限制因子。质谱分析(LC-MS/MS)确定了 DDX5 的重要相互作用伙伴,包括干扰素诱导蛋白 16(IFI16)和多聚核抑制复合体 2(PRC2)的辅助亚基 RBBP4/7。DDX5 与 IFI16、RBBP4/7 和核心 PRC2 亚基共同沉淀在原生核提取物的尺寸排阻色谱分馏物中。DDX5免疫沉淀物的原生凝胶电泳显示了750 kDa的DDX5/IFI16/PRC2复合物,并通过超分辨显微镜进行纳米级共定位验证。先前的研究表明,IFI16 通过与共价闭合环状 DNA(cccDNA)的干扰素敏感反应元件结合,抑制 HBV 转录,从而减少 H3 乙酰化并增加 H3K27me3 水平,其机制尚不清楚。在本文中,我们证明异位表达 IFI16 可抑制重组 rcccDNA 的 HBV 转录,这与 IFI16 与 rcccDNA 结合增加、H3 乙酰化减少以及染色质免疫沉淀法测定的 H3K27me3 升高有关。重要的是,异位 IFI16 对 HBV 转录的抑制作用可被 siRNA 介导的 DDX5 和 EZH2(PRC2 的甲基转移酶亚基)敲除逆转。这种逆转与 IFI16 与 rcccDNA 结合减少、H3 乙酰化增强和 H3K27me3 减少有关。同样,由干扰素-α诱导的内源性 IFI16 以 DDX5 和 PRC2 依赖性方式抑制 HBV rcccDNA 的转录。在 HBV 感染的 HepG2-NTCP 细胞中,当 DDX5 和 EZH2 被敲除时,干扰素-α 的抗病毒作用就会减弱,这说明 DDX5 复合物在 IFI16 介导的抗病毒反应中起着关键作用。总之,在对干扰素做出反应时,DDX5与IFI16合作结合cccDNA,引导PRC2对cccDNA染色质进行表观遗传沉默,从而调节免疫信号转导和HBV转录。
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引用次数: 0
The Effectiveness of COVID-19 Vaccination on Post-Acute Sequelae of SARS-CoV-2 Infection Among Geriatric Patients COVID-19疫苗接种对老年患者SARS-CoV-2感染急性后后遗症的影响
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-16 DOI: 10.1002/jmv.70119
Yi-Ju Chan, Chia-Chen Chen, Yu-Kuan Tu, Wan-Hsuan Hsu, Ya-Wen Tsai, Ting-Hui Liu, Po-Yu Huang, Min-Hsiang Chuang, Kuo-Chuan Hung, Mei-Chuan Lee, Tsung Yu, Chih-Cheng Lai, Tzu-Chieh Weng, Jheng-Yan Wu

This study aims to evaluate the effectiveness of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing the post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as long COVID, and reducing all-cause mortality among older patients. A retrospective cohort study was conducted using the TriNetX database. The study cohort consisted of older patients (age ≥ 65 years) with their first COVID-19 illness between January 1, 2022, and May 31, 2024. Participants were divided into vaccinated and unvaccinated groups based on their vaccination status. Propensity score matching (PSM) was used to balance baseline characteristics. Cox regression models and log-rank tests were applied to estimate the hazard ratio (HR) for PASC and all-cause mortality during 30–180 days of follow-up. The study included 189 059 geriatric patients who contracted SARS-CoV-2, with 5615 vaccinated and 183 444 unvaccinated. After PSM, each group contained 5615 patients. Vaccinated patients exhibited a significantly lower incidence of PASC symptoms (HR = 0.852, 95% CI: 0.778–0.933, p = 0.0005), particularly anxiety and depression, with a HR of 0.710 (95% CI: 0.575–0.878, p = 0.0015). Vaccination was also significantly associated with reduced all-cause mortality (HR = 0.231, 95% CI: 0.136–0.394, p < 0.0001). The findings highlight the effectiveness of COVID-19 vaccination in mitigating the development of PASC and decreasing mortality among older patients.

本研究旨在评估抗严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)疫苗在预防 SARS-CoV-2 感染急性后遗症(PASC)(俗称长 COVID)和降低老年患者全因死亡率方面的效果。我们利用 TriNetX 数据库进行了一项回顾性队列研究。研究队列包括2022年1月1日至2024年5月31日期间首次感染COVID-19的老年患者(年龄≥65岁)。根据疫苗接种情况将参与者分为已接种疫苗组和未接种疫苗组。采用倾向得分匹配法(PSM)平衡基线特征。采用 Cox 回归模型和对数秩检验来估算随访 30-180 天期间 PASC 和全因死亡率的危险比 (HR)。研究纳入了 189059 名感染 SARS-CoV-2 的老年患者,其中 5615 人已接种疫苗,18344 人未接种疫苗。PSM 后,每组各有 5615 名患者。接种疫苗的患者 PASC 症状发生率明显降低(HR = 0.852,95% CI:0.778-0.933,p = 0.0005),尤其是焦虑和抑郁,HR 为 0.710(95% CI:0.575-0.878,p = 0.0015)。接种疫苗也与全因死亡率的降低有很大关系(HR = 0.231,95% CI:0.136-0.394,p = 0.0015)。
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引用次数: 0
Exploring the Role of EBV Infection in EBV-T/NKLPD With EBV Capture Technology Based on Single-Cell RNA Sequencing 利用基于单细胞RNA测序的EBV捕获技术探索EBV感染在EBV- t /NKLPD中的作用。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-16 DOI: 10.1002/jmv.70094
Shunan Wang, Miao Zhong, Wenqi Zhu, Yeqin Sha, Ruize Chen, Hanning Tang, Yongle Li, Huayuan Zhu, Lei Fan
<p>Epstein-Barr virus (EBV)-associated T/NK cell lymphoproliferative diseases (EBV-T/NKLPD) is a highly heterogeneous group of disease, whose clinical manifestations range from an indolent course to aggressive disease, making it challenging to make the concise diagnosis and to decide the best time for allogenic hematopoietic stem-cell transplantation. EBV infection is crucial to the occurrence and development of EBV-T/NKLPD [<span>1</span>]. However, the underestimated morbidity, high heterogeneity and lack of specific cell line make it difficult to decipher the concrete function of EBV in this disease [<span>2</span>].</p><p>Single-cell RNA sequencing (scRNA-seq) detects gene expression in single cell, providing opportunities to dissect cell heterogeneity and the cell-to-cell interaction in tumor microenvironment, which is an excellent tool to analyze the mechanism of virus infection. 10X Genomics and SMART-seq. 2 are two most frequently-used scRNA-seq platforms. 10X Genomics can detect rare cell populations due to high cell throughout. Meanwhile, SMART-seq. 2 can detect more genes, especially low abundance transcripts. The two technologies are complementary and their combination become the dominant mode to study the virus-to-host interaction currently but the high cost is obviously unbearable to most people [<span>3</span>].</p><p>On the basis of 10X Genomics platform (Figure 1A), we added viral probes on the magnetic beads and used secondary enrichment to amplify the titer of EBV (Figure 1B). To evaluate the sensitivity and specificity of this technology, EBV+ Raji cells (<i>n</i> = 727) and EBV− A549 cells (<i>n</i> = 458) were mixed together, and were detected the level of EBV infection (Figure 1C,D). Using traditional 10X Genomics, only 303 (41.7%) Raji cells were tested EBV positive while the updated EBV capture technology detected 723 (99.4%) EBV+ Raji cells (Figure 1E). Obviously, the updated EBV capture technology improved the sensitivity and specificity of virus capturing.</p><p>This updated technology was then used to explore the role of EBV in EBV-T/NKLPD. We collected nasopharyngeal biopsy from one patient diagnosed with extranodal NK/T-cell lymphoma, nasal, as well as cutaneous biopsy from one patient diagnosed with systemic chronic active EBV disease before treatment (Figure 1F and Supporting Information: Figure 1A,B). Although EBV infection existed in all types of cells, the EBV-positive cell proportion (Figure 1G) and CNV score (Figure 1H and Supporting Information: Figure 1C) were the highest in T cells, indicating EBV tropism for T cells. In total cells, EBV+ cells had a higher CNV score compared with EBV− cells, which attributed mainly to the difference between EBV + T cells and EBV− T cells (Figure 1I and Supporting Information: Figure 1D).</p><p>Then we analyzed the gene expression of T cells (<i>n</i> = 1348) and categorized them into three clusters, including naive T cells, NK/T cells and proliferative NK/T cells, which e
eb病毒(EBV)相关T/NK细胞淋巴增生性疾病(EBV-T/NKLPD)是一种高度异质性的疾病,其临床表现从惰性到侵袭性不等,这使得对同种异体造血干细胞移植的精确诊断和最佳时机的确定具有挑战性。EBV感染对EBV- t /NKLPD的发生和发展至关重要。然而,由于发病率被低估,异质性高,缺乏特异性细胞系,使得很难破译EBV在该疾病中的具体功能[2]。单细胞RNA测序(scRNA-seq)检测单细胞内的基因表达,为解剖肿瘤微环境中细胞异质性和细胞间相互作用提供了机会,是分析病毒感染机制的良好工具。10X Genomics和SMART-seq。2是两种最常用的scRNA-seq平台。10X基因组学可以检测到罕见的细胞群体,由于高细胞通透性。与此同时,SMART-seq。2 .可以检测到更多的基因,特别是低丰度转录本。这两种技术是互补的,它们的结合成为目前研究病毒与宿主相互作用的主导模式,但高昂的成本显然是大多数人无法承受的[10]。在10X Genomics平台的基础上(图1A),我们在磁珠上添加病毒探针,并使用二次富集扩增EBV滴度(图1B)。为了评估该技术的敏感性和特异性,将EBV+ Raji细胞(n = 727)和EBV - A549细胞(n = 458)混合在一起,检测EBV感染水平(图1C,D)。使用传统的10X Genomics,只有303个(41.7%)Raji细胞检测到EBV阳性,而更新的EBV捕获技术检测到723个(99.4%)EBV+ Raji细胞(图1E)。显然,更新后的EBV捕获技术提高了病毒捕获的敏感性和特异性。这项更新的技术随后被用于探索EBV在EBV- t /NKLPD中的作用。我们在治疗前收集了一名诊断为结外NK/ t细胞淋巴瘤的患者的鼻咽活检,以及一名诊断为全身性慢性活动性EBV疾病的患者的鼻腔和皮肤活检(图1F和支持信息:图1A,B)。虽然EBV感染存在于所有类型的细胞中,但EBV阳性细胞比例(图1G)和CNV评分(图1H和支持信息:图1C)在T细胞中最高,表明EBV对T细胞有趋向性。在总细胞中,EBV+细胞的CNV评分高于EBV -细胞,这主要归因于EBV+ T细胞和EBV - T细胞之间的差异(图1I和支持信息:图1D)。然后,我们分析了T细胞(n = 1348)的基因表达,并将其分为三组,包括幼稚T细胞、NK/T细胞和增殖NK/T细胞,这体现了T细胞群体的功能异质性(图2A)。三种类型的T细胞均存在EBV感染。增殖NK/T细胞中EBV阳性细胞、EBV高表达细胞和平均EBV负荷比例均最高(图2B-E)。在T细胞中,EBV负荷与CNV评分呈正相关,特别是在增殖性NK/T细胞中,这表明EBV感染诱导的基因组不稳定性(图2G和支持信息:图1E)。通过对EBV+细胞和EBV -细胞的基因集富集分析(GSEA)发现,不同细胞中富集的途径不同,表明对EBV的敏感性不同。增殖相关的信号通路,包括E2F靶点、G2M检查点和MYC靶点信号通路,在EBV + T细胞中富集(图2F),特别是在EBV负担高的增殖性NK/T细胞中(支持信息:图2A,B)。伪时间轨迹分析显示EBV感染在所有类型T细胞的进化过程中持续存在(支持信息:图3A)。随着EBV负荷的增加,增殖相关信号通路和基因的表达增加(支持信息:图3B,C)。EBV感染后,幼稚T细胞和NK/T细胞的干性评分升高,而增殖NK/T细胞的干性评分相反(support Information: Figure 3D)。在其他细胞类型中,代谢相关途径,包括氧化磷酸化、脂肪生成、柠檬酸循环、半胱氨酸和蛋氨酸代谢,在EBV+细胞中明显富集(支持信息:图3E)。脂肪酸和糖酵解相关基因的氧化在增殖性NK/T细胞中有明显的增加趋势,进一步表明EBV对代谢的影响(支持信息:图3F)。细胞间通讯分析显示,EBV + T细胞与其他细胞的相互作用最多、最强(图2H)。 在增殖性NK/T细胞中,EBV -细胞与单核细胞的相互作用明显强于EBV+细胞(图2I)。在初始T细胞中,EBV+细胞与内皮细胞或B细胞之间的相互作用明显强于EBV−细胞(图2I)。结果表明,基于单细胞RNA测序的新型EBV捕获技术是研究EBV作用的实用技术。在T细胞中,EBV感染促进细胞增殖、基因组不稳定、干性增加以及与其他细胞的相互作用。这可能解释EBV在EBV- t /NKLPD中的致癌机制。然而,受样本量小的限制,我们的结果需要通过多中心、大规模队列来验证。王淑楠和钟淼设计了研究,并收集和分析了数据。王淑楠提供了一份手稿草稿。朱文琪、沙叶琴、陈瑞泽参与数据校正和分析。李永乐和唐汉宁采集临床样本。王顺南、朱华远和范磊提供了资金。朱华远和范磊监督了这项研究。雷凡审阅并修改了手稿。所有作者都阅读并批准了最终的手稿。南京医科大学江苏省医院伦理委员会批准本研究(No. 2024-SRFA-693)。在为涉及人体组织的实验收集任何样本之前,必须获得每位患者的知情同意。作者声明无利益冲突。
{"title":"Exploring the Role of EBV Infection in EBV-T/NKLPD With EBV Capture Technology Based on Single-Cell RNA Sequencing","authors":"Shunan Wang,&nbsp;Miao Zhong,&nbsp;Wenqi Zhu,&nbsp;Yeqin Sha,&nbsp;Ruize Chen,&nbsp;Hanning Tang,&nbsp;Yongle Li,&nbsp;Huayuan Zhu,&nbsp;Lei Fan","doi":"10.1002/jmv.70094","DOIUrl":"10.1002/jmv.70094","url":null,"abstract":"&lt;p&gt;Epstein-Barr virus (EBV)-associated T/NK cell lymphoproliferative diseases (EBV-T/NKLPD) is a highly heterogeneous group of disease, whose clinical manifestations range from an indolent course to aggressive disease, making it challenging to make the concise diagnosis and to decide the best time for allogenic hematopoietic stem-cell transplantation. EBV infection is crucial to the occurrence and development of EBV-T/NKLPD [&lt;span&gt;1&lt;/span&gt;]. However, the underestimated morbidity, high heterogeneity and lack of specific cell line make it difficult to decipher the concrete function of EBV in this disease [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Single-cell RNA sequencing (scRNA-seq) detects gene expression in single cell, providing opportunities to dissect cell heterogeneity and the cell-to-cell interaction in tumor microenvironment, which is an excellent tool to analyze the mechanism of virus infection. 10X Genomics and SMART-seq. 2 are two most frequently-used scRNA-seq platforms. 10X Genomics can detect rare cell populations due to high cell throughout. Meanwhile, SMART-seq. 2 can detect more genes, especially low abundance transcripts. The two technologies are complementary and their combination become the dominant mode to study the virus-to-host interaction currently but the high cost is obviously unbearable to most people [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;On the basis of 10X Genomics platform (Figure 1A), we added viral probes on the magnetic beads and used secondary enrichment to amplify the titer of EBV (Figure 1B). To evaluate the sensitivity and specificity of this technology, EBV+ Raji cells (&lt;i&gt;n&lt;/i&gt; = 727) and EBV− A549 cells (&lt;i&gt;n&lt;/i&gt; = 458) were mixed together, and were detected the level of EBV infection (Figure 1C,D). Using traditional 10X Genomics, only 303 (41.7%) Raji cells were tested EBV positive while the updated EBV capture technology detected 723 (99.4%) EBV+ Raji cells (Figure 1E). Obviously, the updated EBV capture technology improved the sensitivity and specificity of virus capturing.&lt;/p&gt;&lt;p&gt;This updated technology was then used to explore the role of EBV in EBV-T/NKLPD. We collected nasopharyngeal biopsy from one patient diagnosed with extranodal NK/T-cell lymphoma, nasal, as well as cutaneous biopsy from one patient diagnosed with systemic chronic active EBV disease before treatment (Figure 1F and Supporting Information: Figure 1A,B). Although EBV infection existed in all types of cells, the EBV-positive cell proportion (Figure 1G) and CNV score (Figure 1H and Supporting Information: Figure 1C) were the highest in T cells, indicating EBV tropism for T cells. In total cells, EBV+ cells had a higher CNV score compared with EBV− cells, which attributed mainly to the difference between EBV + T cells and EBV− T cells (Figure 1I and Supporting Information: Figure 1D).&lt;/p&gt;&lt;p&gt;Then we analyzed the gene expression of T cells (&lt;i&gt;n&lt;/i&gt; = 1348) and categorized them into three clusters, including naive T cells, NK/T cells and proliferative NK/T cells, which e","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epidemiological, Clinical, and Genomic Traits of PIV in Hospitalized Children After the COVID-19 Pandemic in Wuhan, China 武汉新冠肺炎大流行后住院儿童PIV的流行病学、临床和基因组特征
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-14 DOI: 10.1002/jmv.70117
Jiaming Huang, Ying Li, Hebin Chen, Haizhou Liu, Wenqing Li, Ismaila Damilare Isiaka, Hui Du, Muhammad Noman, Muhammad Arif Rizwan, Qing Du, Yang Li, Yaxin Lin, Yuehu Liu, Xiaoxia Lu, Di Liu, Yi Yan

Human parainfluenza virus (PIV) is a main cause of acute lower respiratory tract infections (ALRTIs), which contributes to childrens' mortality worldwide; however, the epidemiology of PIVs following the SARS-CoV-2 pandemic is still not clarified, and poses risks of potential outbreaks. Herein, we conducted a retrospective observational study from September 26, 2020 to September 30, 2023 to assess PIV epidemiology in Wuhan, China, as well as the clinical characteristics of PIV infections. In total, 14,065 inpatients with ALRTIs were enrolled, of which 936 were identified to have PIV infection. We also obtained 69 PIV3 RNA to reveal its molecular traits. An alteration in PIV season pattern away from spring and summer prevalence was noted, as well as a progressive rise in its detection rate. PIV-related ALRTIs were more prevalent in male patients. PIV3 was the dominant PIV type in recent years. In comparison with the phase before the cancellation of Dynamic Zero-COVID Policy in December 2022, symptoms after its repeal were milder. All Wuhan strains were classified with C3f lineage and possibly evolved from native strains in China. Additionally, some mutations, such as Q499P in protein hemagglutinin-neuraminidase, should be given further attention. In summary, our study demonstrates the clinical characteristics of PIVs and genomic traits of PIV3 in Wuhan, China, thus holds importance for the diagnosis and control of PIV infections in the post-pandemic era.

人副流感病毒(PIV)是急性下呼吸道感染(ALRTIs)的主要原因,这是造成全世界儿童死亡的原因之一;然而,在SARS-CoV-2大流行之后,piv的流行病学仍不清楚,并构成潜在疫情的风险。在此,我们进行了2020年9月26日至2023年9月30日的回顾性观察研究,以评估中国武汉的PIV流行病学以及PIV感染的临床特征。共纳入14065例alrti住院患者,其中936例确诊为PIV感染。我们还获得了69个PIV3 RNA以揭示其分子特征。注意到PIV季节模式的改变,远离春季和夏季流行,以及其检出率的逐步上升。piv相关的ALRTIs在男性患者中更为普遍。PIV3是近年来主要的PIV类型。与2022年12月取消动态零冠政策之前的阶段相比,废除后的症状要温和得多。所有武汉毒株均属于C3f谱系,可能由中国本土毒株进化而来。此外,一些突变,如血凝素-神经氨酸酶蛋白Q499P,应给予进一步的关注。综上所述,我们的研究揭示了中国武汉地区PIV的临床特征和PIV3的基因组特征,因此对后大流行时代PIV感染的诊断和控制具有重要意义。
{"title":"Epidemiological, Clinical, and Genomic Traits of PIV in Hospitalized Children After the COVID-19 Pandemic in Wuhan, China","authors":"Jiaming Huang,&nbsp;Ying Li,&nbsp;Hebin Chen,&nbsp;Haizhou Liu,&nbsp;Wenqing Li,&nbsp;Ismaila Damilare Isiaka,&nbsp;Hui Du,&nbsp;Muhammad Noman,&nbsp;Muhammad Arif Rizwan,&nbsp;Qing Du,&nbsp;Yang Li,&nbsp;Yaxin Lin,&nbsp;Yuehu Liu,&nbsp;Xiaoxia Lu,&nbsp;Di Liu,&nbsp;Yi Yan","doi":"10.1002/jmv.70117","DOIUrl":"10.1002/jmv.70117","url":null,"abstract":"<p>Human parainfluenza virus (PIV) is a main cause of acute lower respiratory tract infections (ALRTIs), which contributes to childrens' mortality worldwide; however, the epidemiology of PIVs following the SARS-CoV-2 pandemic is still not clarified, and poses risks of potential outbreaks. Herein, we conducted a retrospective observational study from September 26, 2020 to September 30, 2023 to assess PIV epidemiology in Wuhan, China, as well as the clinical characteristics of PIV infections. In total, 14,065 inpatients with ALRTIs were enrolled, of which 936 were identified to have PIV infection. We also obtained 69 PIV3 RNA to reveal its molecular traits. An alteration in PIV season pattern away from spring and summer prevalence was noted, as well as a progressive rise in its detection rate. PIV-related ALRTIs were more prevalent in male patients. PIV3 was the dominant PIV type in recent years. In comparison with the phase before the cancellation of Dynamic Zero-COVID Policy in December 2022, symptoms after its repeal were milder. All Wuhan strains were classified with C3f lineage and possibly evolved from native strains in China. Additionally, some mutations, such as Q499P in protein hemagglutinin-neuraminidase, should be given further attention. In summary, our study demonstrates the clinical characteristics of PIVs and genomic traits of PIV3 in Wuhan, China, thus holds importance for the diagnosis and control of PIV infections in the post-pandemic era.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unusual G9P[4] Rotavirus Emerged After the Dynamic Changes in Rotavirus Genotypes From Equine-Like G3 to Typical Human G1/G3 in Indonesia 印度尼西亚轮状病毒基因型从马类G3到典型人类G1/G3发生动态变化后,出现了不寻常的G9P[4]轮状病毒。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-13 DOI: 10.1002/jmv.70106
Zayyin Dinana, Yen Hai Doan, Aussie Tahta Maharani, Anisa Lailatul Fitria, Laura Navika Yamani,  Juniastuti, Rury Mega Wahyuni, Soegeng Soegijanto,  Soetjipto, Takako Utsumi, Chieko Matsui, Lin Deng, Nobuhiro Takemae, Tsutomu Kageyama, Kazuhiko Katayama, Maria Inge Lusida, Ikuo Shoji

Inter-genogroup reassortment of Rotavirus A (RVA) strains has highlighted the spread of unusual RVA strains worldwide. We previously reported the equine-like G3 RVA as the predominant strain in Indonesia in 2015–2016. However, since July 2017, typical human genotypes G1 and G3 have replaced these strains completely. To understand how dynamic changes in RVA occur in Indonesia, we performed a detailed epidemiological study. A total of 356 stool specimens were collected from hospitalized children in Sidoarjo, Indonesia between 2018 and 2022. Whole-genome sequencing was performed for all 26 RVA-positive samples using next-generation sequencing. Twenty-four samples were determined to be the unusual RVA G9P[4], while two were G9P[6]. Detailed analysis revealed that seven G9P[4] strains had the typical DS-1-like backbone, while the other strains exhibited a double-reassortant profile (G9-N1) on the DS-1-like backbone. The Bayesian evolutionary analyses suggested that the Indonesian G9P[4] strains share a common ancestor with previously reported G9P[4] strains in the VP7 and VP4 genes. G9P[4] DS-1-like strains were identified as the predominant genotype in Indonesia in 2021 for the first time. These results suggest that the G9P[4] strains were generated from the previous G9P[4] strains that had undergone further intra-reassortments with the other circulating strains.

A 型轮状病毒(RVA)毒株的基因组间重组突显了不寻常 RVA 毒株在全球范围内的传播。我们之前曾报道,2015-2016 年,印度尼西亚的主要毒株是马科类 G3 RVA。然而,自 2017 年 7 月以来,典型的人类基因型 G1 和 G3 已经完全取代了这些菌株。为了了解印尼 RVA 的动态变化,我们进行了一项详细的流行病学研究。2018 年至 2022 年期间,我们从印度尼西亚锡多阿若的住院儿童中收集了共计 356 份粪便标本。我们使用新一代测序技术对所有 26 份 RVA 阳性样本进行了全基因组测序。24个样本被确定为不常见的RVA G9P[4],2个样本为G9P[6]。详细分析显示,7 株 G9P[4] 具有典型的 DS-1 样性骨架,而其他菌株则在 DS-1 样性骨架上表现出双不重要特征(G9-N1)。贝叶斯进化分析表明,印尼的 G9P[4] 株系与之前报道的 G9P[4] 株系在 VP7 和 VP4 基因上有着共同的祖先。2021 年,G9P[4] DS-1-like 株系首次被确定为印度尼西亚的主要基因型。这些结果表明,G9P[4]菌株是由以前的G9P[4]菌株与其他流通菌株经过进一步内部重组后产生的。
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引用次数: 0
Tick-Borne Encephalitis Virus Surveillance—Vaccination- and Infection-Induced Seroprevalences in Western Austria 2024 2024年奥地利西部蜱传脑炎病毒监测-疫苗接种和感染诱导的血清患病率。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-12-11 DOI: 10.1002/jmv.70109
Anita Siller, Lidia Chitimia-Dobler, Wolfgang Hitzl, Manfred Astl, Harald Schennach, Peter Fraunberger, Janne Cadamuro, Johannes P. Borde, Peter Willeit, Gerhard Dobler, Sylvia Mink

Reported tick-borne-encephalitis (TBE) cases have been increasing in Western Austria, but no data are available on vaccination- and infection-specific seroprevalence. This study aimed to estimate current TBEV-seroprevalence in the region and inform prevention programs by comparing anti-NS1-based-incidence rates with reported case numbers and vaccination coverage. Between December 2023 and February 2024, serum samples from 4619 blood donors in Western Austria were collected and analyzed using TBEV- and WNV-IgG-ELISA assays. Seropositive samples were tested with a TBEV-anti-NS1-IgG-ELISA to distinguish infections from vaccinations. Borderline samples were retested with serum neutralization and triple-NS1-assays. The overall anti-TBEV-IgG-seroprevalence was 80.1% (95%CI 78.9–81.3); 2.7% (95%CI 2.3–3.2) of donors tested positive for anti-TBEV-NS1 IgG antibodies, indicating previous infection. The notified incidence rate in Western Austria was 2.7/100 000/year, compared to 136.2/100 000/year based on anti-TBEV-NS1-seropositive donors, denoting a substantial number of unreported cases (mean manifestation index 1.9%). The number of donors with TBEV-infections varied considerably by district, highlighting potential hotspots for TBEV-infections. The high anti-NS1-based, estimated annual TBE incidence rates show significant differences between districts, highlighting the need for targeted prevention programs. The high rate of undiagnosed TBE cases further suggests that estimated anti-NS1-based incidence rates should be considered when defining high-risk areas.

在西奥地利州,报告的蜱传脑炎(TBE)病例一直在增加,但没有关于疫苗接种和感染特异性血清患病率的数据。该研究旨在通过比较基于抗ns1的发病率与报告的病例数和疫苗接种覆盖率,估计该地区目前的tbev血清患病率,并为预防计划提供信息。在2023年12月至2024年2月期间,收集了西奥地利州4619名献血者的血清样本,并使用TBEV-和WNV-IgG-ELISA检测进行了分析。血清阳性样本用TBEV-anti-NS1-IgG-ELISA检测,以区分感染与疫苗接种。用血清中和和三重ns1试验重新检测临界样品。总抗乙型肝炎病毒igg血清阳性率为80.1% (95%CI 78.9-81.3);2.7% (95%CI 2.3-3.2)的供者抗乙型脑炎病毒ns1 IgG抗体检测呈阳性,提示既往感染。西奥地利州通报的发病率为2.7/10万/年,而基于抗tbev - ns1血清阳性供者的发病率为136.2/10万/年,这表明有大量未报告病例(平均表现指数1.9%)。感染病毒性肝炎病毒的捐助者人数因地区而异,突出了病毒性肝炎病毒感染的潜在热点。高抗ns1为基础,估计每年TBE发病率在地区之间存在显著差异,突出了有针对性的预防方案的必要性。未确诊的TBE病例的高比率进一步表明,在确定高风险区域时应考虑估计的基于抗ns1的发病率。
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Journal of Medical Virology
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