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Embracing Complexity: What Novel Sequencing Methods Are Teaching Us About Herpesvirus Genomic Diversity. 拥抱复杂性:新型测序方法对疱疹病毒基因组多样性的启示》(What Novel Sequencing Methods Are Teaching Us About Herpesvirus Genomic Diversity.
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-06-07 DOI: 10.1146/annurev-virology-100422-010336
Alejandro Ortigas-Vasquez, Moriah Szpara

The arrival of novel sequencing technologies throughout the past two decades has led to a paradigm shift in our understanding of herpesvirus genomic diversity. Previously, herpesviruses were thought to exist as a family of DNA viruses with mostly identical genomes that evolved at much slower rates than RNA viruses. However, a growing body of evidence now suggests that herpesviruses exist as dynamic populations that possess standing variation and evolve at much faster rates than previously assumed. In this review, we explore how strategies such as deep sequencing, long-read sequencing, and haplotype reconstruction are allowing scientists to dissect the genomic composition of herpesvirus populations. We also discuss the challenges that need to be addressed before a detailed picture of herpesvirus diversity can emerge.

过去二十年中,新型测序技术的出现使我们对疱疹病毒基因组多样性的认识发生了范式转变。以前,人们认为疱疹病毒是 DNA 病毒家族的一种,其基因组大多相同,进化速度比 RNA 病毒慢得多。然而,现在越来越多的证据表明,疱疹病毒是作为动态种群存在的,它们拥有恒定的变异,进化速度比以前假设的要快得多。在这篇综述中,我们将探讨深度测序、长序列测序和单体型重建等策略是如何让科学家们剖析疱疹病毒种群的基因组组成的。我们还讨论了在详细了解疱疹病毒多样性之前需要应对的挑战。
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引用次数: 0
Antiviral and Immunomodulatory Effects of Interferon Lambda at the Maternal-Fetal Interface. λ干扰素在母胎界面的抗病毒和免疫调节作用
IF 8.1 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-06-07 DOI: 10.1146/annurev-virology-111821-101531
Margaret R Dedloff, Helen M Lazear

Interferon lambda (IFN-λ, type III IFN, IL-28/29) is a family of antiviral cytokines that are especially important at barrier sites, including the maternal-fetal interface. Recent discoveries have identified important roles for IFN-λ during pregnancy, particularly in the context of congenital infections. Here, we provide a comprehensive review of the activity of IFN-λ at the maternal-fetal interface, highlighting cell types that produce and respond to IFN-λ in the placenta, decidua, and endometrium. Further, we discuss the role of IFN-λ during infections with congenital pathogens including Zika virus, human cytomegalovirus, rubella virus, and Listeria monocytogenes. We discuss advances in experimental models that can be used to fill important knowledge gaps about IFN-λ-mediated immunity.

λ干扰素(IFN-λ,III型IFN,IL-28/29)是抗病毒细胞因子家族的一种,在屏障部位(包括母胎界面)尤其重要。最近的研究发现,IFN-λ 在孕期,尤其是在先天性感染中发挥着重要作用。在此,我们全面回顾了 IFN-λ 在母胎界面的活性,重点介绍了胎盘、蜕膜和子宫内膜中产生 IFN-λ 并对其做出反应的细胞类型。此外,我们还讨论了 IFN-λ 在感染先天性病原体(包括寨卡病毒、人类巨细胞病毒、风疹病毒和李斯特菌)过程中的作用。我们讨论了实验模型的进展,这些模型可用于填补有关 IFN-λ 介导的免疫的重要知识空白。
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引用次数: 0
Bacteriophage T4 as a Protein-Based, Adjuvant- and Needle-Free, Mucosal Pandemic Vaccine Design Platform. 将噬菌体 T4 作为基于蛋白质、无佐剂和无针头的黏膜大流行病疫苗设计平台。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-20 DOI: 10.1146/annurev-virology-111821-111145
Jingen Zhu, Pan Tao, Ashok K Chopra, Venigalla B Rao

The COVID-19 pandemic has transformed vaccinology. Rapid deployment of mRNA vaccines has saved countless lives. However, these platforms have inherent limitations including lack of durability of immune responses and mucosal immunity, high cost, and thermal instability. These and uncertainties about the nature of future pandemics underscore the need for exploring next-generation vaccine platforms. Here, we present a novel protein-based, bacteriophage T4 platform for rapid design of efficacious vaccines against bacterial and viral pathogens. Full-length antigens can be displayed at high density on a 120 × 86 nm phage capsid through nonessential capsid binding proteins Soc and Hoc. Such nanoparticles, without any adjuvant, induce robust humoral, cellular, and mucosal responses when administered intranasally and confer sterilizing immunity. Combined with structural stability and ease of manufacture, T4 phage provides an excellent needle-free, mucosal pandemic vaccine platform and allows equitable vaccine access to low- and middle-income communities across the globe.

COVID-19 大流行改变了疫苗学。mRNA 疫苗的快速应用挽救了无数生命。然而,这些平台存在固有的局限性,包括免疫反应和粘膜免疫缺乏持久性、成本高昂以及热不稳定性。这些问题以及未来大流行病性质的不确定性突出表明了探索下一代疫苗平台的必要性。在这里,我们提出了一种基于蛋白质的新型噬菌体 T4 平台,用于快速设计针对细菌和病毒病原体的高效疫苗。通过非必要的噬菌体结合蛋白 Soc 和 Hoc,全长抗原可以高密度地显示在 120 × 86 nm 的噬菌体外壳上。这种纳米颗粒不含任何佐剂,经鼻内给药后可诱导强有力的体液、细胞和粘膜反应,并赋予灭菌免疫力。T4 噬菌体结构稳定,易于制造,是一种出色的无针粘膜大流行病疫苗平台,可为全球中低收入社区提供公平的疫苗接种机会。
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引用次数: 0
SEA-PHAGES and SEA-GENES: Advancing Virology and Science Education SEA-PHAGES 和 SEA-GENES:推进病毒学和科学教育
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-04-29 DOI: 10.1146/annurev-virology-113023-110757
Danielle M. Heller, Viknesh Sivanathan, David J. Asai, Graham F. Hatfull
Research opportunities for undergraduate students are strongly advantageous, but implementation at a large scale presents numerous challenges. The enormous diversity of the bacteriophage population and a supportive programmatic structure provide opportunities to engage early-career undergraduates in phage discovery, genomics, and genetics. The Science Education Alliance (SEA) is an inclusive Research-Education Community (iREC) providing centralized programmatic support for students and faculty without prior experience in virology at institutions from community colleges to research-active universities to participate in two course-based projects, SEA-PHAGES (SEA Phage Hunters Advancing Genomic and Evolutionary Science) and SEA-GENES (SEA Gene-function Exploration by a Network of Emerging Scientists). Since 2008, the SEA has supported more than 50,000 undergraduate researchers who have isolated more than 23,000 bacteriophages of which more than 4,500 are fully sequenced and annotated. Students have functionally characterized hundreds of phage genes, and the phage collection has fueled the therapeutic use of phages for treatment of Mycobacterium infections. Participation in the SEA promotes student persistence in science education, and its inclusivity promotes a more equitable scientific community.
为本科生提供研究机会是非常有利的,但在大规模实施过程中会遇到许多挑战。噬菌体种群的巨大多样性和支持性的计划结构为早期职业本科生参与噬菌体发现、基因组学和遗传学研究提供了机会。科学教育联盟(SEA)是一个包容性的研究教育社区(iREC),为从社区学院到研究活跃的大学等机构中没有病毒学经验的学生和教师提供集中的项目支持,让他们参与两个基于课程的项目:SEA-PHAGES(SEA Phage Hunters Advancing Genomic and Evolutionary Science)和 SEA-GENES(SEA Gene-function Exploration by a Network of Emerging Scientists)。自 2008 年以来,SEA 已为 50,000 多名本科生研究人员提供了支持,他们分离出了 23,000 多种噬菌体,其中 4,500 多种已完成测序和注释。学生们对数百个噬菌体基因进行了功能定位,噬菌体的收集也促进了噬菌体在治疗分枝杆菌感染方面的应用。参与 SEA 促进了学生对科学教育的坚持,其包容性促进了更公平的科学界。
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引用次数: 0
Controlling Much? Viral Control of Host Chromatin Dynamics 控制了多少?病毒对宿主染色质动力学的控制
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-04-29 DOI: 10.1146/annurev-virology-100422-011616
Laurel E. Kelnhofer-Millevolte, Edward A. Arnold, Daniel H. Nguyen, Daphne C. Avgousti
Viruses are exemplary molecular biologists and have been integral to scientific discovery for generations. It is therefore no surprise that nuclear replicating viruses have evolved to systematically take over host cell function through astoundingly specific nuclear and chromatin hijacking. In this review, we focus on nuclear replicating DNA viruses—herpesviruses and adenoviruses—as key examples of viral invasion in the nucleus. We concentrate on critical features of nuclear architecture, such as chromatin and the nucleolus, to illustrate the complexity of the virus-host battle for resources in the nucleus. We conclude with a discussion of the technological advances that have enabled the discoveries we describe and upcoming steps in this burgeoning field.
病毒是分子生物学家的典范,世世代代都是科学发现不可或缺的一部分。因此,核复制病毒在进化过程中通过令人震惊的特异性核和染色质劫持系统性地接管宿主细胞功能也就不足为奇了。在这篇综述中,我们将重点讨论核复制 DNA 病毒--疱疹病毒和腺病毒--作为病毒入侵细胞核的关键实例。我们将重点放在核结构的关键特征上,如染色质和核仁,以说明病毒与宿主争夺细胞核资源的复杂性。最后,我们讨论了促成我们所述发现的技术进步以及这一新兴领域即将采取的措施。
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引用次数: 0
Abortive Infection of Animal Cells: What Goes Wrong 动物细胞的无效感染:出了什么问题
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-04-18 DOI: 10.1146/annurev-virology-100422-023037
Aaron Embry, Don B. Gammon
Even if a virus successfully binds to a cell, defects in any of the downstream steps of the viral life cycle can preclude the production of infectious virus particles. Such abortive infections are likely common in nature and can provide fundamental insights into the cell and host tropism of viral pathogens. Research over the past 60 years has revealed an incredible diversity of abortive infections by DNA and RNA viruses in various animal cell types. Here we discuss the general causes of abortive infections and provide specific examples from the literature to illustrate the range of abortive infections that have been reported. We also discuss how abortive infections can have critical roles in shaping host immune responses and in the development of virus-induced cancers. Finally, we describe how abortive infections can be applied to basic and clinical research, underscoring the importance of understanding these fascinating aspects of virus biology.
即使病毒成功地与细胞结合,病毒生命周期中任何一个下游步骤的缺陷都可能导致无法产生有传染性的病毒粒子。这种流产感染在自然界中很可能很常见,并能让人们从根本上了解病毒病原体的细胞和宿主趋向性。过去 60 年的研究揭示了 DNA 和 RNA 病毒在各种动物细胞中终止感染的惊人多样性。在此,我们将讨论中止感染的一般原因,并提供文献中的具体实例来说明已报道的中止感染的范围。我们还讨论了终止感染如何在形成宿主免疫反应和发展病毒诱导的癌症中发挥关键作用。最后,我们介绍了中止感染如何应用于基础和临床研究,强调了了解病毒生物学这些迷人方面的重要性。
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引用次数: 0
Rift Valley Fever Virus Encephalitis: Viral and Host Determinants of Pathogenesis 裂谷热病毒脑炎:发病的病毒和宿主决定因素
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-04-18 DOI: 10.1146/annurev-virology-093022-011544
Lindsay R. Wilson, Anita K. McElroy
Rift Valley fever virus (RVFV) is a mosquito-borne virus endemic to Africa and the Middle East. RVFV infection can cause encephalitis, which is associated with significant morbidity and mortality. Studies of RVFV encephalitis following percutaneous inoculation, as would occur following a mosquito bite, have historically been limited by a lack of consistent animal models. In this review, we describe new insights into the pathogenesis of RVFV and the opportunities provided by new mouse models. We underscore the need to consider viral strain and route of inoculation when interpreting data obtained using animal models. We discuss the trafficking of RVFV and the role of host genetics and immunity in modulating the pathogenesis of RVFV encephalitis. We also explore potential strategies to prevent and treat central nervous system disease caused by RVFV and discuss remaining knowledge gaps.
裂谷热病毒(RVFV)是非洲和中东地区流行的一种蚊媒病毒。RVFV 感染可导致脑炎,发病率和死亡率都很高。由于缺乏一致的动物模型,有关经皮接种(如蚊虫叮咬后发生)后 RVFV 脑炎的研究一直受到限制。在这篇综述中,我们描述了对 RVFV 发病机制的新认识以及新的小鼠模型所提供的机会。我们强调,在解释使用动物模型获得的数据时,需要考虑病毒株和接种途径。我们讨论了 RVFV 的贩运以及宿主遗传和免疫在调节 RVFV 脑炎发病机制中的作用。我们还探讨了预防和治疗 RVFV 引起的中枢神经系统疾病的潜在策略,并讨论了尚存在的知识空白。
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引用次数: 0
The Emergence and Evolution of SARS-CoV-2 SARS-CoV-2 的出现和演变
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-04-18 DOI: 10.1146/annurev-virology-093022-013037
Edward C. Holmes
The origin of SARS-CoV-2 has evoked heated debate and strong accusations, yet seemingly little resolution. I review the scientific evidence on the origin of SARS-CoV-2 and its subsequent spread through the human population. The available data clearly point to a natural zoonotic emergence within, or closely linked to, the Huanan Seafood Wholesale Market in Wuhan. There is no direct evidence linking the emergence of SARS-CoV-2 to laboratory work conducted at the Wuhan Institute of Virology. The subsequent global spread of SARS-CoV-2 was characterized by a gradual adaptation to humans, with dual increases in transmissibility and virulence until the emergence of the Omicron variant. Of note has been the frequent transmission of SARS-CoV-2 from humans to other animals, marking it as a strongly host generalist virus. Unless lessons from the origin of SARS-CoV-2 are learned, it is inevitable that more zoonotic events leading to more epidemics and pandemics will plague human populations.
SARS-CoV-2 的起源引起了激烈的争论和强烈的指责,但似乎并没有得到什么解决。我回顾了有关 SARS-CoV-2 起源及其随后在人类中传播的科学证据。现有数据清楚地表明,SARS-CoV-2 是在武汉华南水产品批发市场内自然出现的人畜共患疾病,或与该市场密切相关。没有直接证据表明 SARS-CoV-2 的出现与武汉病毒研究所的实验室工作有关。随后,SARS-CoV-2 在全球的传播特点是逐渐适应人类,传播性和毒力双重增强,直到出现 Omicron 变种。值得注意的是,SARS-CoV-2 经常从人类传染给其他动物,这标志着它是一种具有强烈宿主通性的病毒。除非从 SARS-CoV-2 的起源中吸取教训,否则更多的人畜共患病事件将不可避免地导致更多的流行病和大流行病困扰人类。
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引用次数: 0
The Spectrum of Postacute Sequelae of COVID-19 in Children: From MIS-C to Long COVID 儿童 COVID-19 急性后遗症的范围:从MIS-C到长COVID
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-04-18 DOI: 10.1146/annurev-virology-093022-011839
Abigail S. Kane, Madeleine Godfrey, Magali Noval Rivas, Moshe Arditi, Alessio Fasano, Lael M. Yonker
The effects of SARS-CoV-2 infection on children continue to evolve following the onset of the COVID-19 pandemic. Although life-threatening multisystem inflammatory syndrome in children (MIS-C) has become rare, long-standing symptoms stemming from persistent immune activation beyond the resolution of acute SARS-CoV-2 infection contribute to major health sequelae and continue to pose an economic burden. Shared pathophysiologic mechanisms place MIS-C and long COVID within a vast spectrum of postinfectious conditions characterized by intestinal dysbiosis, increased gut permeability, and varying degrees of immune dysregulation. Insights obtained from MIS-C will help shape our understanding of the more indolent and prevalent postacute sequelae of COVID and ultimately guide efforts to improve diagnosis and management of postinfectious complications of SARS-CoV-2 infection in children.
在 COVID-19 大流行之后,SARS-CoV-2 感染对儿童的影响继续演变。虽然危及生命的儿童多系统炎症综合征(MIS-C)已变得罕见,但在急性 SARS-CoV-2 感染缓解后,由于持续的免疫激活而产生的长期症状会造成严重的健康后遗症,并继续造成经济负担。共同的病理生理学机制将 MIS-C 和长期 COVID 置于以肠道菌群失调、肠道通透性增加和不同程度的免疫失调为特征的大量感染后病症中。从 MIS-C 中获得的启示将有助于我们了解 COVID 更为轻微和普遍的急性后遗症,并最终指导我们改善儿童 SARS-CoV-2 感染后并发症的诊断和管理。
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引用次数: 0
A Mammalian Cell's Guide on How to Process a Bacteriophage. 哺乳动物细胞如何处理噬菌体指南。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2023-09-29 DOI: 10.1146/annurev-virology-111821-111322
Leo Kan, Jeremy J Barr

Bacteriophages are enigmatic entities that defy definition. Classically, they are specialist viruses that exclusively parasitize bacterial hosts. Yet this definition becomes limiting when we consider their ubiquity in the body coupled with their vast capacity to directly interact with the mammalian host. While phages certainly do not infect nor replicate within mammalian cells, they do interact with and gain unfettered access to the eukaryotic cell structure. With the growing appreciation for the human virome, coupled with our increased application of phages to patients within clinical settings, the potential impact of phage-mammalian interactions is progressively recognized. In this review, we provide a detailed mechanistic overview of how phages interact with the mammalian cell surface, the processes through which said phages are internalized by the cell, and the intracellular processing and fate of the phages. We then summarize the current state-of-the-field with respect to phage-mammalian interactions and their associations with health and disease states.

噬菌体是难以定义的神秘实体。通常,它们是专门寄生在细菌宿主身上的病毒。然而,当我们考虑到它们在体内的普遍性,以及它们与哺乳动物宿主直接相互作用的巨大能力时,这个定义就变得有限了。虽然噬菌体肯定不会感染哺乳动物细胞,也不会在哺乳动物细胞内复制,但它们确实与真核细胞结构相互作用,并获得不受限制的进入途径。随着人们对人类病毒组的日益重视,加上我们在临床环境中对患者应用噬菌体的增加,噬菌体与哺乳动物相互作用的潜在影响逐渐得到认识。在这篇综述中,我们提供了噬菌体如何与哺乳动物细胞表面相互作用的详细机制概述,所述噬菌体被细胞内化的过程,以及噬菌体的细胞内处理和命运。然后,我们总结了该领域关于噬菌体-哺乳动物相互作用及其与健康和疾病状态的关系的现状。
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引用次数: 0
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Annual Review of Virology
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