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RNA-Based Vaccination of Plants for Control of Viruses. 基于rna的植物预防病毒的研究。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-091919-073708
Andreas E Voloudakis, Athanasios Kaldis, Basavaprabhu L Patil

Plant viruses cause nearly half of the emerging plant diseases worldwide, contributing to 10-15% of crop yield losses. Control of plant viral diseases is mainly accomplished by extensive chemical applications targeting the vectors (i.e., insects, nematodes, fungi) transmitting these viruses. However, these chemicals have a significant negative effect on human health and the environment. RNA interference is an endogenous, cellular, sequence-specific RNA degradation mechanism in eukaryotes induced by double-stranded RNA molecules that has been exploited as an antiviral strategy through transgenesis. Because genetically modified crop plants are not accepted for cultivation in several countries globally, there is an urgent demand for alternative strategies. This has boosted research on exogenous application of the RNA-based biopesticides that are shown to exhibit significant protective effect against viral infections. Such environment-friendly and efficacious antiviral agents for crop protection will contribute to global food security, without adverse effects on human health.

植物病毒造成了全世界近一半的新发植物病害,造成了10-15%的作物产量损失。植物病毒性疾病的控制主要是通过针对传播这些病毒的媒介(即昆虫、线虫、真菌)的广泛化学应用来实现的。然而,这些化学品对人类健康和环境有重大的负面影响。RNA干扰是真核生物中由双链RNA分子诱导的内源性、细胞性、序列特异性RNA降解机制,已被利用为通过转基因的抗病毒策略。由于转基因作物在全球一些国家不被接受种植,因此迫切需要替代策略。这促进了基于rna的生物农药外源性应用的研究,这些生物农药显示出对病毒感染的显着保护作用。这种环境友好和有效的作物保护抗病毒药物将有助于全球粮食安全,而不会对人类健康产生不利影响。
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引用次数: 6
A Trait-Based Approach to Predicting Viral Host-Range Evolvability. 基于性状的病毒宿主进化预测方法。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-091919-092003
Hannah M Strobel, Elizabeth C Stuart, Justin R Meyer

Predicting the evolution of virus host range has proven to be extremely difficult, in part because of the sheer diversity of viruses, each with unique biology and ecological interactions. We have not solved this problem, but to make the problem more tractable, we narrowed our focus to three traits intrinsic to all viruses that may play a role in host-range evolvability: mutation rate, recombination rate, and phenotypic heterogeneity. Although each trait should increase evolvability, they cannot do so unbounded because fitness trade-offs limit the ability of all three traits to maximize evolvability. By examining these constraints, we can begin to identify groups of viruses with suites of traits that make them especially concerning, as well as ecological and environmental conditions that might push evolution toward accelerating host-range expansion.

预测病毒宿主范围的演变已被证明是极其困难的,部分原因是病毒的多样性,每一种病毒都有独特的生物和生态相互作用。我们还没有解决这个问题,但为了使问题更容易处理,我们将研究范围缩小到可能在宿主进化中发挥作用的所有病毒固有的三个特征:突变率、重组率和表型异质性。虽然每个特征都应该增加可进化性,但它们不能无限地这样做,因为适应度权衡限制了所有三个特征最大化可进化性的能力。通过检查这些限制,我们可以开始识别具有一系列特征的病毒组,这些特征使它们特别令人担忧,以及可能推动进化加速宿主范围扩展的生态和环境条件。
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引用次数: 2
APOBEC3: Friend or Foe in Human Papillomavirus Infection and Oncogenesis? APOBEC3:人类乳头瘤病毒感染和肿瘤发生中的朋友还是敌人?
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 Epub Date: 2022-06-07 DOI: 10.1146/annurev-virology-092920-030354
Cody J Warren, Mario L Santiago, Dohun Pyeon

Human papillomavirus (HPV) infection is a causative agent of multiple human cancers, including cervical and head and neck cancers. In these HPV-positive tumors, somatic mutations are caused by aberrant activation of DNA mutators such as members of the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytidine deaminases. APOBEC3 proteins are most notable for their restriction of various viruses, including anti-HPV activity. However, the potential role of APOBEC3 proteins in HPV-induced cancer progression has recently garnered significant attention. Ongoing research stems from the observations that elevated APOBEC3 expression is driven by HPV oncogene expression and that APOBEC3 activity is likely a significant contributor to somatic mutagenesis in HPV-positive cancers. This review focuses on recent advances in the study of APOBEC3 proteins and their roles in HPV infection and HPV-driven oncogenesis. Further, we discuss critical gaps and unanswered questions in our understanding of APOBEC3 in virus-associated cancers.

人乳头瘤病毒(HPV)感染是多种人类癌症的病原体,包括宫颈癌和头颈癌。在这些HPV阳性肿瘤中,体细胞突变是由DNA突变子的异常激活引起的,例如胞苷脱氨酶的载脂蛋白B信使RNA编辑酶催化多肽样3(APOBEC3)家族的成员。APOBEC3蛋白最显著的是其对各种病毒的限制,包括抗HPV活性。然而,APOBEC3蛋白在HPV诱导的癌症进展中的潜在作用最近引起了人们的广泛关注。正在进行的研究源于以下观察结果,即APOBEC3表达的升高是由HPV癌基因表达驱动的,并且APOBEC3活性可能是HPV阳性癌症体细胞突变的重要因素。本文综述了APOBEC3蛋白及其在HPV感染和HPV驱动的肿瘤发生中的作用的研究进展。此外,我们还讨论了我们对病毒相关癌症中APOBEC3的理解中的关键差距和未回答的问题。
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引用次数: 7
Systems Biology of Virus-Host Protein Interactions: From Hypothesis Generation to Mechanisms of Replication and Pathogenesis. 病毒-宿主蛋白相互作用的系统生物学:从假说的产生到复制和发病机制。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-100520-011851
Priya S Shah, Nitin S Beesabathuni, Adam T Fishburn, Matthew W Kenaston, Shiaki A Minami, Oanh H Pham, Inglis Tucker

As obligate intracellular parasites, all viruses must co-opt cellular machinery to facilitate their own replication. Viruses often co-opt these cellular pathways and processes through physical interactions between viral and host proteins. In addition to facilitating fundamental aspects of virus replication cycles, these virus-host protein interactions can also disrupt physiological functions of host proteins, causing disease that can be advantageous to the virus or simply a coincidence. Consequently, unraveling virus-host protein interactions can serve as a window into molecular mechanisms of virus replication and pathogenesis. Identifying virus-host protein interactions using unbiased systems biology approaches provides an avenue for hypothesis generation. This review highlights common systems biology approaches for identification of virus-host protein interactions and the mechanistic insights revealed by these methods. We also review conceptual innovations using comparative and integrative systems biology that can leverage global virus-host protein interaction data sets to more rapidly move from hypothesis generation to mechanism.

作为专性细胞内寄生虫,所有病毒都必须利用细胞机制来促进自身的复制。病毒通常通过病毒和宿主蛋白之间的物理相互作用来利用这些细胞途径和过程。除了促进病毒复制周期的基本方面外,这些病毒-宿主蛋白质相互作用还可以破坏宿主蛋白质的生理功能,导致对病毒有利的疾病或仅仅是巧合。因此,解开病毒与宿主蛋白的相互作用可以作为了解病毒复制和发病机制的分子机制的窗口。使用无偏系统生物学方法鉴定病毒-宿主蛋白相互作用为假设生成提供了一条途径。这篇综述强调了鉴定病毒-宿主蛋白相互作用的常见系统生物学方法以及这些方法揭示的机制见解。我们还回顾了使用比较和综合系统生物学的概念创新,这些概念创新可以利用全球病毒-宿主蛋白相互作用数据集,更快地从假设生成转向机制。
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引用次数: 4
Liquid Phase Partitioning in Virus Replication: Observations and Opportunities. 病毒复制中的液相划分:观察结果和机会。
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2022-09-29 Epub Date: 2022-06-16 DOI: 10.1146/annurev-virology-093020-013659
Chao Wu, Alex S Holehouse, Daisy W Leung, Gaya K Amarasinghe, Rebecca Ellis Dutch

Viruses frequently carry out replication in specialized compartments within cells. The effect of these structures on virus replication is poorly understood. Recent research supports phase separation as a foundational principle for organization of cellular components with the potential to influence viral replication. In this review, phase separation is described in the context of formation of viral replication centers, with an emphasis on the nonsegmented negative-strand RNA viruses. Consideration is given to the interplay between phase separation and the critical processes of viral transcription and genome replication, and the role of these regions in pathogen-host interactions is discussed. Finally, critical questions that must be addressed to fully understand how phase separation influences viral replication and the viral life cycle are presented, along with information about new approaches that could be used to make important breakthroughs in this emerging field.

病毒经常在细胞内的特殊隔间中进行复制。人们对这些结构对病毒复制的影响知之甚少。最近的研究支持将相分离作为组织可能影响病毒复制的细胞成分的基本原则。在这篇综述中,相分离是在病毒复制中心形成的背景下描述的,重点是非片段负链RNA病毒。考虑了相分离与病毒转录和基因组复制的关键过程之间的相互作用,并讨论了这些区域在病原体-宿主相互作用中的作用。最后,介绍了为了充分了解相分离如何影响病毒复制和病毒生命周期而必须解决的关键问题,以及可用于在这一新兴领域取得重要突破的新方法的信息。《病毒学年度评论》第9卷预计最终在线出版日期为2022年9月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 0
Lessons from Acquired Natural Immunity and Clinical Trials to Inform Next-Generation Human Cytomegalovirus Vaccine Development. 获得性自然免疫和临床试验的经验教训,为下一代人类巨细胞病毒疫苗的开发提供信息。
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2022-09-29 Epub Date: 2022-06-15 DOI: 10.1146/annurev-virology-100220-010653
Xintao Hu, Hsuan-Yuan Wang, Claire E Otero, Jennifer A Jenks, Sallie R Permar

Human cytomegalovirus (HCMV) infection, the most common cause of congenital disease globally, affecting an estimated 1 million newborns annually, can result in lifelong sequelae in infants, such as sensorineural hearing loss and brain damage. HCMV infection also leads to a significant disease burden in immunocompromised individuals. Hence, an effective HCMV vaccine is urgently needed to prevent infection and HCMV-associated diseases. Unfortunately, despite more than five decades of vaccine development, no successful HCMV vaccine is available. This review summarizes what we have learned from acquired natural immunity, including innate and adaptive immunity; the successes and failures of HCMV vaccine human clinical trials; the progress in related animal models; and the analysis of protective immune responses during natural infection and vaccination settings. Finally, we propose novel vaccine strategies that will harness the knowledge of protective immunity and employ new technology and vaccine concepts to inform next-generation HCMV vaccine development.

人类巨细胞病毒(HCMV)感染是全球最常见的先天性疾病原因,每年影响约100万新生儿,可能导致婴儿终身后遗症,如感音神经性听力损失和脑损伤。HCMV感染也会导致免疫功能受损个体的重大疾病负担。因此,迫切需要一种有效的HCMV疫苗来预防感染和HCMV相关疾病。不幸的是,尽管已经开发了50多年的疫苗,但还没有成功的HCMV疫苗。这篇综述总结了我们从获得性自然免疫中学到的东西,包括先天免疫和适应性免疫;HCMV疫苗人体临床试验的成功与失败;相关动物模型的进展;以及在自然感染和疫苗接种环境中保护性免疫反应的分析。最后,我们提出了新的疫苗策略,将利用保护性免疫的知识,并利用新技术和疫苗概念为下一代HCMV疫苗的开发提供信息。
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引用次数: 0
Replication Compartments of Eukaryotic and Bacterial DNA Viruses: Common Themes Between Different Domains of Host Cells. 真核生物和细菌DNA病毒的复制区室:宿主细胞不同区域之间的共同主题。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-012822-125828
David M Knipe, Amy Prichard, Surendra Sharma, Joe Pogliano

Subcellular organization is essential for life. Cells organize their functions into organelles to concentrate their machinery and supplies for optimal efficiency. Likewise, viruses organize their replication machinery into compartments or factories within their host cells for optimal replicative efficiency. In this review, we discuss how DNA viruses that infect both eukaryotic cells and bacteria assemble replication compartments for synthesis of progeny viral DNA and transcription of the viral genome. Eukaryotic DNA viruses assemble replication compartments in the nucleus of the host cell while DNA bacteriophages assemble compartments called phage nuclei in the bacterial cytoplasm. Thus, DNA viruses infecting host cells from different domains of life share common replication strategies.

亚细胞组织是生命所必需的。细胞将其功能组织到细胞器中,以集中其机器和供应以达到最佳效率。同样地,病毒将它们的复制机制组织成宿主细胞内的隔间或工厂,以获得最佳的复制效率。在这篇综述中,我们讨论了感染真核细胞和细菌的DNA病毒如何组装复制室来合成子代病毒DNA和转录病毒基因组。真核DNA病毒在宿主细胞核中组装复制室,而DNA噬菌体在细菌细胞质中组装称为噬菌体核的室。因此,感染来自不同生命域的宿主细胞的DNA病毒具有共同的复制策略。
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引用次数: 11
Amoebae: Hiding in Plain Sight: Unappreciated Hosts for the Very Large Viruses. 变形虫:隐藏在显眼的地方:超大病毒未被发现的宿主。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-100520-125832
Victória Fulgêncio Queiroz, Rodrigo Araújo Lima Rodrigues, Paulo Victor de Miranda Boratto, Bernard La Scola, Julien Andreani, Jônatas Santos Abrahão

For decades, viruses have been isolated primarily from humans and other organisms. Interestingly, one of the most complex sides of the virosphere was discovered using free-living amoebae as hosts. The discovery of giant viruses in the early twenty-first century opened a new chapter in the field of virology. Giant viruses are included in the phylum Nucleocytoviricota and harbor large and complex DNA genomes (up to 2.7 Mb) encoding genes never before seen in the virosphere and presenting gigantic particles (up to 1.5 μm). Different amoebae have been used to isolate and characterize a plethora of new viruses with exciting details about novel viral biology. Through distinct isolation techniques and metagenomics, the diversity and complexity of giant viruses have astonished the scientific community. Here, we discuss the latest findings on amoeba viruses and how using these single-celled organisms as hosts has revealed entities that have remained hidden in plain sight for ages.

几十年来,病毒主要是从人类和其他生物体中分离出来的。有趣的是,人们发现病毒圈最复杂的一面是使用自由生活的变形虫作为宿主。21世纪初巨型病毒的发现开启了病毒学领域的新篇章。巨型病毒包括在核细胞病毒门中,具有大而复杂的DNA基因组(高达2.7 Mb),编码病毒圈中从未见过的基因,并呈现巨大的颗粒(高达1.5 μm)。不同的变形虫被用来分离和表征大量的新病毒,并提供了关于新病毒生物学的令人兴奋的细节。通过不同的分离技术和宏基因组学,巨型病毒的多样性和复杂性震惊了科学界。在这里,我们讨论关于变形虫病毒的最新发现,以及如何使用这些单细胞生物作为宿主揭示了多年来一直隐藏在视线之外的实体。
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引用次数: 6
Advances in Understanding Neuropathogenesis of Rift Valley Fever Virus. 裂谷热病毒神经发病机制的研究进展
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-091919-065806
Kaleigh A Connors, Amy L Hartman
Rift Valley fever virus (RVFV) is an emerging arboviral pathogen that causes disease in both livestock and humans. Severe disease manifestations of Rift Valley fever (RVF) in humans include hemorrhagic fever, ocular disease, and encephalitis. This review describes the current understanding of the pathogenesis of RVF encephalitis. While some data from human studies exist, the development of several animal models has accelerated studies of the neuropathogenesis of RVFV. We review current animal models and discuss what they have taught us about RVFV encephalitis. We briefly describe alternative models that have been used to study other neurotropic arboviruses and how these models may help contribute to our understanding RVFV encephalitis. We conclude with some unanswered questions and future directions.
裂谷热病毒(RVFV)是一种新出现的虫媒病毒病原体,可在牲畜和人类中引起疾病。裂谷热(RVF)在人类中的严重疾病表现包括出血热、眼病和脑炎。本文综述了目前对裂谷热脑炎发病机制的了解。虽然存在一些来自人类研究的数据,但几种动物模型的发展加速了对裂谷热病毒神经发病机制的研究。我们回顾了目前的动物模型并讨论了它们教给我们的关于裂谷热病毒脑炎的知识。我们简要描述了用于研究其他嗜神经虫媒病毒的替代模型,以及这些模型如何有助于我们了解裂谷热病毒脑炎。最后,我们提出了一些悬而未决的问题和未来的发展方向。
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引用次数: 10
Cyclic Nucleotide Signaling in Phage Defense and Counter-Defense. 环状核苷酸信号在噬菌体防御和反防御中的作用。
IF 11.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-100120-010228
Januka S Athukoralage, Malcolm F White

Advances in our understanding of prokaryotic antiphage defense mechanisms in the past few years have revealed a multitude of new cyclic nucleotide signaling molecules that play a crucial role in switching infected cells into an antiviral state. Defense pathways including type III CRISPR (clustered regularly interspaced palindromic repeats), CBASS (cyclic nucleotide-based antiphage signaling system), PYCSAR (pyrimidine cyclase system for antiphage resistance), and Thoeris all use cyclic nucleotides as second messengers to activate a diverse range of effector proteins. These effectors typically degrade or disrupt key cellular components such as nucleic acids, membranes, or metabolites, slowing down viral replication kinetics at great cost to the infected cell. Mechanisms to manipulate the levels of cyclic nucleotides are employed by cells to regulate defense pathways and by viruses to subvert them. Here we review the discovery and mechanism of the key pathways, signaling molecules and effectors, parallels and differences between the systems, open questions, and prospects for future research in this area.

在过去的几年中,我们对原核噬菌体防御机制的理解取得了进展,揭示了许多新的环核苷酸信号分子,它们在将感染细胞转换为抗病毒状态方面起着至关重要的作用。包括III型CRISPR(聚集规律间隔的回文重复序列)、CBASS(基于环核苷酸的噬菌体信号系统)、PYCSAR(用于抗噬菌体抗性的嘧啶环化酶系统)和Thoeris在内的防御途径都使用环核苷酸作为第二信使来激活多种效应蛋白。这些效应物通常降解或破坏关键的细胞成分,如核酸、膜或代谢物,以极大的代价减慢病毒复制动力学。细胞利用控制环核苷酸水平的机制来调节防御途径,病毒利用这种机制来破坏防御途径。在此,我们综述了关键通路的发现和机制、信号分子和效应器、系统之间的相似之处和差异、悬而未决的问题以及该领域未来研究的前景。
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引用次数: 26
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Annual Review of Virology
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