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Genomic Characterization of Three Canadian Mumps Outbreaks Demonstrates Endemic Transmission in Canada 加拿大三次腮腺炎疫情的基因组特征表明加拿大存在地方性传播
Pub Date : 2024-08-10 DOI: 10.3390/v16081280
Jasmine Rae Frost, Grace Eunchong Seo, Kerry Dust, Jared Bullard, Peter Daley, Jason J. LeBlanc, Joanne Hiebert, Elizabeth McLachlan, Alberto Severini
Despite the provision of a mumps vaccination program in Canada for over three decades, mumps has not reached elimination. Instead, a re-emergence has been observed in vaccinated populations, particularly in young adults. These outbreaks have been almost exclusively due to genotype G infections, a trend that has been seen in other countries with high mumps vaccination rates. To characterize mumps outbreaks in Canada, genomes from samples from Manitoba (n = 209), Newfoundland (n = 25), and Nova Scotia (n = 48) were sequenced and analysed by Bayesian inference. Whole genome sequencing was shown to be highly discriminatory for outbreak investigations compared to traditional Sanger sequencing. The results showed that mumps virus genotype G most likely circulated endemically in Canada and between Canada and the US. Overall, this Canadian outbreak data from different provinces and ancestral strains demonstrates the benefits of molecular genomic data to better characterize mumps outbreaks, but also suggests genomics could further our understanding of the reasons for potential immune escape of mumps genotype G and evolution in highly vaccinated populations. With a possible endemic circulation of mumps genotype G and the remaining risk of new imported cases, increased surveillance and alternative vaccination strategies may be required for Canada to reach the current target for mumps or a future elimination status.
尽管加拿大实施流行性腮腺炎疫苗接种计划已有三十多年,但流行性腮腺炎并没有绝迹。相反,在接种过疫苗的人群中,尤其是青壮年中,腮腺炎再次出现。这些疫情几乎完全是由基因型 G 感染引起的,这一趋势也出现在流行性腮腺炎疫苗接种率较高的其他国家。为了描述加拿大流行性腮腺炎疫情的特点,对来自马尼托巴省(n = 209)、纽芬兰省(n = 25)和新斯科舍省(n = 48)的样本进行了基因组测序,并通过贝叶斯推断法进行了分析。结果表明,与传统的桑格测序法相比,全基因组测序法在疫情调查中具有很高的鉴别力。结果表明,腮腺炎病毒基因型 G 最有可能在加拿大以及加拿大和美国之间流行。总之,来自不同省份和祖先毒株的加拿大疫情数据表明了分子基因组数据对更好地描述流行性腮腺炎疫情的益处,同时也表明基因组学可以进一步帮助我们了解流行性腮腺炎基因型 G 的潜在免疫逃逸和在高度接种人群中进化的原因。由于流行性腮腺炎基因型 G 可能会在地方流行,而且仍有可能出现新的输入病例,因此加拿大可能需要加强监测并采取替代疫苗接种策略,以实现当前或未来消灭流行性腮腺炎的目标。
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引用次数: 0
Help or Hinder: Protein Host Factors That Impact HIV-1 Replication 帮助还是阻碍?影响 HIV-1 复制的蛋白质宿主因子
Pub Date : 2024-08-10 DOI: 10.3390/v16081281
Michael Rameen Moezpoor, Mario Stevenson
Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell’s susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of the HIV-1 replication cycle, contributing to productive infection and replication, or severely attenuating the chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to the various HIV-1 target cell types where appropriate.
人体免疫缺陷病毒 1 型(HIV-1)与其宿主因子或目标细胞的限制因子之间的相互作用决定了细胞对感染的易感性和感染的结果。细胞固有的因子参与了 HIV-1 复制周期的每一个步骤,这些因子有的促进了有成效的感染和复制,有的则严重降低了感染成功的几率。此外,某些细胞类型所特有的因素也会导致这些细胞类型之间的感染差异。了解这些参与 HIV-1 感染的因素是开发抗 HIV-1 疗法的关键要求。随着各种因素的不断增加,这些因素与病毒之间的动态相互作用也得到了阐明,因此,全面而最新的总结将有助于该领域的研究,它将展示已知的知识,以便研究人员在他人的基础上研究未知的知识。在此,我们旨在提供一篇综述,重点介绍在复制周期的每个阶段以积极或消极的方式影响 HIV-1 复制的蛋白质宿主因子,包括众所周知的和相对较新的因子,并在适当的地方强调各种 HIV-1 靶细胞类型所特有的因子。
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引用次数: 0
Human Stimulator of Interferon Genes Promotes Rhinovirus C Replication in Mouse Cells In Vitro and In Vivo 人干扰素基因刺激器促进鼻病毒 C 在小鼠细胞中的体外和体内复制
Pub Date : 2024-08-10 DOI: 10.3390/v16081282
Monty E. Goldstein, Maxinne A. Ignacio, Jeffrey M. Loube, Matthew R. Whorton, Margaret A. Scull
Rhinovirus C (RV-C) infects airway epithelial cells and is an important cause of acute respiratory disease in humans. To interrogate the mechanisms of RV-C-mediated disease, animal models are essential. Towards this, RV-C infection was recently reported in wild-type (WT) mice, yet, titers were not sustained. Therefore, the requirements for RV-C infection in mice remain unclear. Notably, prior work has implicated human cadherin-related family member 3 (CDHR3) and stimulator of interferon genes (STING) as essential host factors for virus uptake and replication, respectively. Here, we report that even though human (h) and murine (m) CDHR3 orthologs have similar tissue distribution, amino acid sequence homology is limited. Further, while RV-C can replicate in mouse lung epithelial type 1 (LET1) cells and produce infectious virus, we observed a significant increase in the frequency and intensity of dsRNA-positive cells following hSTING expression. Based on these findings, we sought to assess the impact of hCDHR3 and hSTING on RV-C infection in mice in vivo. Thus, we developed hCDHR3 transgenic mice, and utilized adeno-associated virus (AAV) to deliver hSTING to the murine airways. Subsequent challenge of these mice with RV-C15 revealed significantly higher titers 24 h post-infection in mice expressing both hCDHR3 and hSTING—compared to either WT mice, or mice with hCDHR3 or hSTING alone, indicating more efficient infection. Ultimately, this mouse model can be further engineered to establish a robust in vivo model, recapitulating viral dynamics and disease.
鼻病毒 C(RV-C)会感染气道上皮细胞,是导致人类急性呼吸道疾病的重要原因。要研究 RV-C 介导疾病的机制,动物模型至关重要。为此,最近有报道称野生型(WT)小鼠感染了 RV-C,但滴度并不持久。因此,小鼠感染 RV-C 的条件仍不清楚。值得注意的是,之前的研究发现人类粘连蛋白相关家族成员 3(CDHR3)和干扰素基因刺激因子(STING)分别是病毒吸收和复制的重要宿主因子。在这里,我们报告说,尽管人(h)和鼠(m)CDHR3 的同源物具有相似的组织分布,但氨基酸序列的同源性却很有限。此外,虽然 RV-C 可以在小鼠肺上皮 1 型(LET1)细胞中复制并产生传染性病毒,但我们观察到 hSTING 表达后 dsRNA 阳性细胞的频率和强度显著增加。基于这些发现,我们试图评估 hCDHR3 和 hSTING 对小鼠体内 RV-C 感染的影响。因此,我们开发了 hCDHR3 转基因小鼠,并利用腺相关病毒 (AAV) 将 hSTING 送入小鼠呼吸道。随后用 RV-C15 挑战这些小鼠,发现同时表达 hCDHR3 和 hSTING 的小鼠在感染后 24 小时的滴度明显高于 WT 小鼠或仅表达 hCDHR3 或 hSTING 的小鼠,这表明感染效率更高。最终,这种小鼠模型可以进一步改造,以建立一个强大的体内模型,重现病毒动态和疾病。
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引用次数: 0
HIV, HCV and HIV-HCV Coinfections in the General Population versus Inmates from Romania 普通人群与罗马尼亚囚犯的艾滋病毒、丙型肝炎病毒和艾滋病毒-丙型肝炎病毒合并感染情况
Pub Date : 2024-08-10 DOI: 10.3390/v16081279
Camelia Sultana, Carmine Falanga, Grațiana Chicin, Laurențiu Ion, Camelia Grancea, Daniela Chiriac, Adriana Iliescu, Andrea Gori
The objective of this study was to analyze the epidemiological links of the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15–87 years who took part in the Open Test Project. They were divided in two subgroups: general population vs. individuals from prisons who were questioned about multiple risk factors. A chi-square independence test was used to establish correlations between risk factors and results of screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug users (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with IDUs (the strongest association), unprotected sex with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.
本研究的目的是分析人类免疫缺陷病毒(HIV)、丙型肝炎病毒(HCV)和 HIV-HCV 合并感染与某些人群中研究较少的传播类型之间的流行病学联系。我们对参加开放测试项目的 903 名 15-87 岁患者进行了前瞻性观察研究。他们被分为两个亚组:普通人群与来自监狱的个人,后者被询问了多种风险因素。采用卡方独立性检验来确定风险因素与筛查结果之间的相关性。根据每个独立的风险因素和年龄,采用逻辑回归法计算出筛查试验出现反应的概率。艾滋病毒与以下因素密切相关:与艾滋病毒呈阳性的伴侣进行无保护性交(关联性最强)、与性工作者进行无保护性交、新诊断出的性传播疾病(STDs)、静脉注射吸毒者(IDUs)和共用注射材料。就丙型肝炎病毒(HCV)反应性检测而言,与注射吸毒者(关联性最强)、与注射吸毒者发生无保护性行为和共用注射材料之间的关联性非常强。我们的研究表明,有必要根据当地的流行病学情况实施有针对性的公共卫生计划,最终在该地区消除肝炎和艾滋病毒感染。
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引用次数: 0
Polysubstance Use and Related Risk Behaviors among People Who Inject Drugs in Kenya Preparing for Hepatitis C Virus Treatment 肯尼亚准备接受丙型肝炎病毒治疗的注射吸毒者的多种物质使用和相关风险行为
Pub Date : 2024-08-10 DOI: 10.3390/v16081277
Lindsey R. Riback, Mercy Nyakowa, John A. Lizcano, Chenshu Zhang, Peter Cherutich, Ann E. Kurth, Matthew J. Akiyama
Polysubstance use (PSU), injection drug use (IDU), and equipment sharing are associated with bloodborne infection (BBI) transmission risk, particularly Hepatitis C Virus (HCV), yet data on PSU in low- and middle-income countries (LMICs) is limited. We report on baseline PSU, medication-assisted treatment (MAT) engagement, and motivation to reduce IDU among 95 people who inject drugs (PWID) who accessed needle and syringe programs (NSP) in Nairobi and Coastal Kenya prior to HCV treatment. Bivariate and multivariate logistic regression were used to examine the associations between PSU and behaviors that confer HCV transmission and acquisition risks. Most participants (70.5%) reported PSU in the last 30 days, and one-third (35.8%) reported PSU exclusive to just heroin and cannabis use. Common combinations were heroin and cannabis (49.3%), and heroin, cannabis, and bugizi (flunitrazepam) (29.9%). Participants at baseline were receiving MAT (69.5%), already stopped or reduced IDU (30.5%), and were HIV-positive (40%). PSU was significantly associated with IDU (p = 0.008) and the number of times (p = 0.016) and days (p = 0.007) injected in the last 30 days. Participants reported high PSU and equipment sharing, despite high MAT engagement. While co-locating BBI treatment within existing harm reduction services is necessary to promote uptake and curb re-infection, tailored services may be needed to address PSU, particularly in LMICs.
多物质使用(PSU)、注射吸毒(IDU)和共用设备与血源性感染(BBI)传播风险有关,尤其是丙型肝炎病毒(HCV),但中低收入国家(LMICs)有关多物质使用的数据非常有限。我们报告了内罗毕和肯尼亚沿海地区 95 名注射吸毒者(PWID)在接受丙型肝炎病毒(HCV)治疗前接受针头和注射器计划(NSP)治疗的基线 PSU、药物辅助治疗(MAT)参与情况以及减少注射吸毒的动机。研究采用了二元和多元逻辑回归法来检验 PSU 与具有 HCV 传播和感染风险的行为之间的关联。大多数参与者(70.5%)报告在过去 30 天内吸食过 PSU,三分之一(35.8%)报告仅吸食过海洛因和大麻。常见的组合是海洛因和大麻(49.3%),以及海洛因、大麻和bugizi(氟硝西泮)(29.9%)。基线参与者正在接受 MAT(69.5%),已经停止或减少 IDU(30.5%),并且艾滋病毒呈阳性(40%)。PSU与IDU(p = 0.008)、过去30天内注射次数(p = 0.016)和天数(p = 0.007)有明显关联。尽管 MAT 的参与率很高,但参与者报告的 PSU 和设备共享率却很高。虽然在现有的减低危害服务中将生物替代治疗放在同一地点对促进接受治疗和遏制再感染是必要的,但可能需要定制服务来解决PSU问题,尤其是在低收入和中等收入国家。
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引用次数: 0
Characterization and Anti-Biofilm Activity of Lytic Enterococcus Phage vB_Efs8_KEN04 against Clinical Isolates of Multidrug-Resistant Enterococcus faecalis in Kenya 溶菌性肠球菌噬菌体 vB_Efs8_KEN04 针对肯尼亚耐多药粪肠球菌临床分离株的特性和抗生物膜活性
Pub Date : 2024-08-09 DOI: 10.3390/v16081275
Oumarou Soro, Collins Kigen, A. Nyerere, Moses Gachoya, Martin Georges, Erick Odoyo, L. Musila
Enterococcus faecalis (E. faecalis) is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04, isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR E. faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between −80 °C and 37 °C. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G + C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that phage vB_Efs8_KEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.
粪肠球菌(Enterococcus faecalis,E. faecalis)是造成医院内感染和耐抗生素感染的一个日益严重的原因。治疗耐药粪肠球菌需要新的方法。使用噬菌体(phages)来对付耐多药(MDR)细菌最近引起了全球关注。生物膜在粪大肠杆菌的致病过程中起着至关重要的作用,因为生物膜会增强抗生素耐药性。噬菌体通过产生溶解酶(包括解聚酶)来消除生物膜。在这项研究中,从肯尼亚内罗毕污水处理厂分离出来的肠球菌噬菌体 vB_Efs8_KEN04 针对 MDR 粪绿球菌的临床菌株进行了测试。该噬菌体对 100%(26/26)的 MDR 粪肠球菌临床分离株具有广泛的宿主范围,对粪肠球菌具有跨物种活性。它能够耐受 pH 值为 3 至 11 的酸性和碱性条件,以及 -80 °C 至 37 °C 的温度。它能抑制和破坏 MDR 粪肠球菌的生物膜。它的线性双链 DNA 基因组长达 142 402 bp,包含 238 个编码序列,G + C 含量和编码基因密度分别为 36.01% 和 91.46%。基因组分析表明,vB_Efs8_KEN04噬菌体属于Herelleviridae科Kochikohdavirus属。它缺乏抗菌素抗性、毒力和裂解基因,其稳定性、广泛的宿主范围和跨物种裂解表明它具有治疗肠球菌感染的强大潜力。
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引用次数: 0
The Role of Wild Boar as Host of Japanese Encephalitis Virus in the Absence of Domestic Pigs 在没有家猪的情况下野猪作为日本脑炎病毒宿主的作用
Pub Date : 2024-08-09 DOI: 10.3390/v16081273
Fuka Kikuchi, Ai Hayashi, Karen Yamada, Yusuke Matsui, Reiko Shimbashi, Yuji Noguchi, Kazunori Tachibana, Tetsuya Mizutani, Akihiko Tokaji, Akira Yoshikawa, Motoki Ihara, Kazunori Oishi, Hajime Kamiya, Satoru Arai, Motoi Suzuki
Pigs are the most common amplifying hosts of the Japanese encephalitis virus (JEV). In 2016, four residents on Tsushima Island who did not own pig farms were diagnosed with JE. Therefore, a serosurvey was conducted to estimate the risk and seroprevalence of JEV after the outbreak. Sera collected from 560 Tsushima Island residents between January and September 2017 were tested for neutralizing antibodies against JEV strains JaGAr01 (genotype 3) and Muar (genotype 5). Sera collected from six wild boars between June and July 2022 were tested. The seroprevalence rates of neutralizing antibodies against JaGAr01 and Muar were 38.8% and 24.6%, respectively. High anti-JEV neutralizing antibody titers of ≥320 were identified in 16 residents, including 3 younger than 6 years with prior JEV vaccination, 2 in their 40s, and 11 older than 70. However, no anti-JEV-specific IgM was detected. Residents who engaged in outdoor activities had higher anti-JEV antibody titers. Sera from wild boars were negative for JEV RNA, but four of six samples contained neutralizing antibodies against JEV. Therefore, JEV transmission continues on Tsushima Island, even in the absence of pig farms, and wild boars might serve as the amplifying hosts.
猪是日本脑炎病毒(JEV)最常见的扩增宿主。2016 年,对马岛上有四名不拥有养猪场的居民被诊断出患有日本脑炎。因此,我们在疫情爆发后进行了血清调查,以估计日本脑炎病毒的风险和血清流行率。对 2017 年 1 月至 9 月期间从 560 名对马岛居民采集的血清进行了 JEV 株 JaGAr01(基因型 3)和 Muar(基因型 5)中和抗体检测。对 2022 年 6 月至 7 月间从 6 头野猪身上采集的血清进行了检测。JaGAr01和Muar的中和抗体血清阳性率分别为38.8%和24.6%。16 名居民的抗 JEV 中和抗体滴度≥320,其中 3 人年龄小于 6 岁,曾接种过 JEV 疫苗,2 人 40 多岁,11 人 70 多岁。但是,没有检测到抗 JEV 特异性 IgM。从事户外活动的居民的抗 JEV 抗体滴度较高。野猪血清中的 JEV RNA 呈阴性,但 6 份样本中有 4 份含有针对 JEV 的中和抗体。因此,即使没有养猪场,对马岛上的 JEV 传播仍在继续,野猪可能是扩大传播的宿主。
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引用次数: 0
No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis 没有时间死亡:巨细胞病毒如何抑制细胞凋亡、坏死和裂解
Pub Date : 2024-08-09 DOI: 10.3390/v16081272
Yingqi Deng, Ana Águeda-Pinto, W. Brune
Viruses are obligate intracellular pathogens as their replication depends on the metabolism of the host cell. The induction of cellular suicide, known as programmed cell death (PCD), has the potential to hinder viral replication and act as a first line of defense against viral pathogens. Apoptosis, necroptosis, and pyroptosis are three important PCD modalities. Different signaling pathways are involved in their execution, and they also differ in their ability to cause inflammation. Cytomegaloviruses (CMV), beta-herpesviruses with large double-stranded DNA genomes, encode a great variety of immune evasion genes, including several cell death suppressors. While CMV inhibitors of apoptosis and necroptosis have been known and studied for years, the first pyroptosis inhibitor has been identified and characterized only recently. Here, we describe how human and murine CMV interfere with apoptosis, necroptosis, and pyroptosis signaling pathways. We also discuss the importance of the different PCD forms and their viral inhibitors for the containment of viral replication and spread in vivo.
病毒是强制性细胞内病原体,因为它们的复制依赖于宿主细胞的新陈代谢。诱导细胞自杀,即所谓的细胞程序性死亡(PCD),有可能阻碍病毒复制,成为抵御病毒病原体的第一道防线。细胞凋亡、坏死和热凋亡是三种重要的 PCD 模式。它们参与执行的信号通路不同,引起炎症的能力也不同。巨细胞病毒(CMV)是具有大型双链 DNA 基因组的β-疱疹病毒,编码多种免疫逃避基因,包括几种细胞死亡抑制因子。虽然 CMV 的细胞凋亡和坏死抑制因子已被人们熟知并研究多年,但首个热凋亡抑制因子直到最近才被发现并定性。在这里,我们描述了人类和小鼠 CMV 如何干扰细胞凋亡、坏死和热凋亡信号通路。我们还讨论了不同的 PCD 形式及其病毒抑制剂对遏制病毒复制和体内传播的重要性。
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引用次数: 0
Detection of Dengue Virus 1 and Mammalian Orthoreovirus 3, with Novel Reassortments, in a South African Family Returning from Thailand, 2017 2017 年在一个从泰国回国的南非家庭中检测到登革病毒 1 和哺乳动物直肠病毒 3,并发现了新的重配病毒
Pub Date : 2024-08-09 DOI: 10.3390/v16081274
Petrus Jansen van Vuren, Rhys H. Parry, J. T. Pawęska
In July 2017, a family of three members, a 46-year-old male, a 45-year-old female and their 8-year-old daughter, returned to South Africa from Thailand. They presented symptoms consistent with mosquito-borne diseases, including fever, headache, severe body aches and nausea. Mosquito bites in all family members suggested recent exposure to arthropod-borne viruses. Dengue virus 1 (Genus Orthoflavivirus) was isolated (isolate no. SA397) from the serum of the 45-year-old female via intracerebral injection in neonatal mice and subsequent passage in VeroE6 cells. Phylogenetic analysis of this strain indicated close genetic identity with cosmopolitan genotype 1 DENV1 strains from Southeast Asia, assigned to major lineage K, minor lineage 1 (DENV1I_K.1), such as GZ8H (99.92%) collected in November 2018 from China, and DV1I-TM19-74 isolate (99.72%) identified in Bangkok, Thailand, in 2019. Serum samples from the 46-year-old male yielded a virus isolate that could not be confirmed as DENV1, prompting unbiased metagenomic sequencing for virus identification and characterization. Illumina sequencing identified multiple segments of a mammalian orthoreovirus (MRV), designated as Human/SA395/SA/2017. Genomic and phylogenetic analyses classified Human/SA395/SA/2017 as MRV-3 and assigned a tentative genotype, MRV-3d, based on the S1 segment. Genomic analyses suggested that Human/SA395/SA/2017 may have originated from reassortments of segments among swine, bat, and human MRVs. The closest identity of the viral attachment protein σ1 (S1) was related to a human isolate identified from Tahiti, French Polynesia, in 1960. This indicates ongoing circulation and co-circulation of Southeast Asian and Polynesian strains, but detailed knowledge is hampered by the limited availability of genomic surveillance. This case represents the rare concurrent detection of two distinct viruses with different transmission routes in the same family with similar clinical presentations. It highlights the complexity of diagnosing diseases with similar sequelae in travelers returning from tropical areas.
2017 年 7 月,一家三口(46 岁男性、45 岁女性及其 8 岁女儿)从泰国返回南非。他们出现了与蚊子传播疾病一致的症状,包括发烧、头痛、全身剧痛和恶心。所有家庭成员都被蚊子叮咬过,这表明他们最近接触过节肢动物传播的病毒。通过对新生小鼠进行脑内注射,并随后在 VeroE6 细胞中培养,从这名 45 岁女性的血清中分离出登革热病毒 1(正黄病毒属)(分离株编号 SA397)。该毒株的系统发育分析表明,它与东南亚的世界性基因型1 DENV1毒株具有密切的遗传一致性,被归入主要品系K,次要品系1(DENV1I_K.1),如2018年11月从中国采集的GZ8H(99.92%),以及2019年在泰国曼谷发现的DV1I-TM19-74分离株(99.72%)。从这名 46 岁男性的血清样本中分离出的病毒无法确认为 DENV1,这促使人们进行无偏见的元基因组测序,以确定病毒的身份和特征。Illumina测序确定了哺乳动物正交病毒(MRV)的多个片段,命名为Human/SA395/SA/2017。基因组学和系统发生学分析将Human/SA395/SA/2017归类为MRV-3,并根据S1片段确定了暂定基因型MRV-3d。基因组分析表明,Human/SA395/SA/2017可能源于猪、蝙蝠和人类MRV之间的片段重组。病毒附着蛋白σ1(S1)与 1960 年在法属波利尼西亚塔希提岛发现的人类分离物的特征最为接近。这表明东南亚和波利尼西亚的病毒株正在流通或共同流通,但由于基因组监测手段有限,无法详细了解其情况。本病例是罕见的在同一家庭中同时发现两种不同传播途径的病毒,且临床表现相似的病例。它凸显了从热带地区返回的旅行者诊断具有类似后遗症的疾病的复杂性。
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引用次数: 0
The Altered Neonatal CD8+ T Cell Immunodominance Hierarchy during Influenza Virus Infection Impacts Peptide Vaccination 流感病毒感染过程中新生儿 CD8+ T 细胞免疫优势层次的改变对多肽疫苗接种的影响
Pub Date : 2024-08-09 DOI: 10.3390/v16081271
Luke Heil, Samantha Jewell, J. Lines, Beth A. Garvy
Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality and delayed clearance of the virus. Generating effective CD8+ T cell responses may be important for improving vaccination outcomes in vulnerable populations, but neonatal T cells frequently respond differently than adult cells. We sought to understand CD8+ T cell specificity and immunodominance during neonatal influenza infection and how any differences from the adult hierarchy might impact peptide vaccine effectiveness. Neonatal C57BL/6 mice displayed an altered CD8+ T cell immunodominance hierarchy during influenza infection, preferentially responding to an epitope in the influenza protein PA rather than the co-dominant adult response to NP and PA. Heterosubtypic infections in mice first infected as pups also displayed altered immunodominance and reduced protection compared to mice first infected as adults. Adoptive transfer of influenza-infected bone-marrow-derived dendritic cells promoted an NP-specific CD8+ T cell response in influenza-virus-infected pups and increased viral clearance. Finally, pups responded to PA (224–233), but not NP (366–374) during peptide vaccination. PA (224–233)-vaccinated mice were not protected during viral challenge. Epitope usage should be considered when designing vaccines that target T cells when the intended patient population includes infants and adults.
与成人相比,新生儿更容易感染流感病毒,导致发病率和死亡率增加,病毒清除延迟。产生有效的 CD8+ T 细胞反应对于改善易感人群的疫苗接种效果可能很重要,但新生儿 T 细胞的反应往往与成人细胞不同。我们试图了解新生儿感染流感期间 CD8+ T 细胞的特异性和免疫优势,以及与成人层次结构的差异会如何影响多肽疫苗的效果。新生 C57BL/6 小鼠在流感感染期间显示出改变的 CD8+ T 细胞免疫优势等级,优先对流感蛋白 PA 中的一个表位做出反应,而不是成人对 NP 和 PA 的共同优势反应。与成年小鼠首次感染相比,幼鼠首次感染时的异亚型感染也显示出免疫优势的改变和保护能力的降低。通过收养性转移感染流感的骨髓树突状细胞,促进了感染流感病毒的幼鼠对NP特异性CD8+ T细胞的反应,并提高了病毒清除率。最后,在多肽疫苗接种过程中,幼崽对 PA(224-233)有反应,而对 NP(366-374)没有反应。接种过 PA (224-233) 疫苗的小鼠在病毒挑战中没有保护作用。在设计靶向 T 细胞的疫苗时,如果目标患者群体包括婴儿和成人,则应考虑表位的使用。
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