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Seeing Biomolecular Condensates Through the Lens of Viruses. 从病毒的视角看生物分子凝聚态。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-04-11 DOI: 10.1146/annurev-virology-111821-103226
Alexander Borodavka, Julia Acker

Phase separation of viral biopolymers is a key factor in the formation of cytoplasmic viral inclusions, known as sites of virus replication and assembly. This review describes the mechanisms and factors that affect phase separation in viral replication and identifies potential areas for future research. Drawing inspiration from studies on cellular RNA-rich condensates, we compare the hierarchical coassembly of ribosomal RNAs and proteins in the nucleolus to the coordinated coassembly of viral RNAs and proteins taking place within viral factories in viruses containing segmented RNA genomes. We highlight the common characteristics of biomolecular condensates in viral replication and how this new understanding is reshaping our views of virus assembly mechanisms. Such studies have the potential to uncover unexplored antiviral strategies targeting these phase-separated states.

病毒生物聚合物的相分离是细胞质病毒内含物形成的关键因素,细胞质病毒内含体被称为病毒复制和组装位点。这篇综述描述了影响病毒复制中相分离的机制和因素,并确定了未来研究的潜在领域。从对富含RNA的细胞缩合物的研究中获得灵感,我们将核糖体RNA和蛋白质在细胞核中的分级共组装与病毒RNA和蛋白质的协同共组装进行了比较,这些协同组装发生在含有分段RNA基因组的病毒的病毒工厂中。我们强调了病毒复制中生物分子缩合物的共同特征,以及这种新的理解如何重塑我们对病毒组装机制的看法。这些研究有可能揭示针对这些相分离状态的未探索的抗病毒策略。
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引用次数: 1
Immunomodulation by Enteric Viruses. 肠道病毒的免疫调节。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-06-28 DOI: 10.1146/annurev-virology-111821-112317
Lucie Bernard-Raichon, Ken Cadwell

Enteric viruses display intricate adaptations to the host mucosal immune system to successfully reproduce in the gastrointestinal tract and cause maladies ranging from gastroenteritis to life-threatening disease upon extraintestinal dissemination. However, many viral infections are asymptomatic, and their presence in the gut is associated with an altered immune landscape that can be beneficial or adverse in certain contexts. Genetic variation in the host and environmental factors including the bacterial microbiota influence how the immune system responds to infections in a remarkably viral strain-specific manner. This immune response, in turn, determines whether a given virus establishes acute versus chronic infection, which may have long-lasting consequences such as susceptibility to inflammatory disease. In this review, we summarize our current understanding of the mechanisms involved in the interaction between enteric viruses and the immune system that underlie the impact of these ubiquitous infectious agents on our health.

肠道病毒对宿主粘膜免疫系统表现出复杂的适应能力,从而在胃肠道中成功繁殖,并在肠道外传播时引发从肠胃炎到危及生命的疾病等疾病。然而,许多病毒感染是无症状的,它们在肠道中的存在与免疫环境的改变有关,在某些情况下可能是有益的,也可能是不利的。宿主的遗传变异和包括细菌微生物群在内的环境因素影响免疫系统如何以显著的病毒株特异性方式对感染做出反应。这种免疫反应反过来决定了特定病毒是建立急性感染还是慢性感染,这可能会产生长期的后果,如对炎症疾病的易感性。在这篇综述中,我们总结了我们目前对肠道病毒和免疫系统之间相互作用机制的理解,这些机制是这些无处不在的传染源对我们健康影响的基础。
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引用次数: 0
A Glimpse into the Past: What Ancient Viral Genomes Reveal About Human History. 回顾过去:古代病毒基因组揭示了人类历史。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-06-02 DOI: 10.1146/annurev-virology-111821-123859
Axel A Guzmán-Solís, Miguel Alejandro Navarro, María C Ávila-Arcos, Daniel Blanco-Melo
Humans have battled viruses for millennia. However, directly linking the symptomatology of disease outbreaks to specific viral pathogens was not possible until the twentieth century. With the advent of the genomic era and the development of advanced protocols for isolation, sequencing, and analysis of ancient nucleic acids from diverse human remains, the identification and characterization of ancient viruses became feasible. Recent studies have provided invaluable information about past epidemics and made it possible to examine assumptions and inferences on the origin and evolution of certain viral families. In parallel, the study of ancient viruses also uncovered their importance in the evolution of the human lineage and their key roles in shaping major events in human history. In this review, we describe the strategies used for the study of ancient viruses, along with their limitations, and provide a detailed account of what past viral infections have revealed about human history. Expected final online publication date for the Annual Review of Virology, Volume 10 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
几千年来,人类一直在与病毒作斗争。然而,直到二十世纪才可能将疾病爆发的症状学与特定的病毒病原体直接联系起来。随着基因组时代的到来,以及从不同人类遗骸中分离、测序和分析古代核酸的先进方案的发展,鉴定和表征古代病毒变得可行。最近的研究提供了关于过去流行病的宝贵信息,并使人们有可能检验关于某些病毒家族起源和进化的假设和推断。与此同时,对古代病毒的研究也揭示了它们在人类谱系进化中的重要性,以及它们在塑造人类历史重大事件中的关键作用。在这篇综述中,我们描述了用于研究古代病毒的策略及其局限性,并详细介绍了过去的病毒感染揭示了人类历史。
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引用次数: 0
Impact of the Microbiota on Viral Infections. 微生物群对病毒感染的影响。
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-04-18 DOI: 10.1146/annurev-virology-111821-115754
Danielle E Campbell, Yuhao Li, Harshad Ingle, Megan T Baldridge

The mammalian gastrointestinal tract (GIT) hosts a diverse and highly active microbiota composed of bacteria, eukaryotes, archaea, and viruses. Studies of the GIT microbiota date back more than a century, although modern techniques, including mouse models, sequencing technology, and novel therapeutics in humans, have been foundational to our understanding of the roles of commensal microbes in health and disease. Here, we review the impacts of the GIT microbiota on viral infection, both within the GIT and systemically. GIT-associated microbes and their metabolites alter the course of viral infection through a variety of mechanisms, including direct interactions with virions, alteration of the GIT landscape, and extensive regulation of innate and adaptive immunity. Mechanistic understanding of the full breadth of interactions between the GIT microbiota and the host is still lacking in many ways but will be vital for the development of novel therapeutics for viral and nonviral diseases alike.

哺乳动物胃肠道(GIT)拥有由细菌、真核生物、古菌和病毒组成的多样且高度活跃的微生物群。对GIT微生物群的研究可以追溯到一个多世纪前,尽管包括小鼠模型、测序技术和人类新疗法在内的现代技术是我们理解共生微生物在健康和疾病中作用的基础。在这里,我们回顾了GIT微生物群对病毒感染的影响,包括在GIT内和系统内。GIT相关微生物及其代谢产物通过多种机制改变病毒感染过程,包括与病毒粒子的直接相互作用、GIT景观的改变以及先天免疫和适应性免疫的广泛调节。对GIT微生物群和宿主之间的全方位相互作用的机制理解在许多方面仍然缺乏,但对于开发治疗病毒性和非病毒性疾病的新疗法至关重要。
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引用次数: 0
Cross-Kingdom Interactions Between Plant and Fungal Viruses. 植物和真菌病毒之间的跨王国相互作用。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-07-05 DOI: 10.1146/annurev-virology-111821-122539
Ida Bagus Andika, Mengyuan Tian, Ruiling Bian, Xinran Cao, Ming Luo, Hideki Kondo, Liying Sun

The large genetic and structural divergences between plants and fungi may hinder the transmission of viruses between these two kingdoms to some extent. However, recent accumulating evidence from virus phylogenetic analyses and the discovery of naturally occurring virus cross-infection suggest the occurrence of past and current transmissions of viruses between plants and plant-associated fungi. Moreover, artificial virus inoculation experiments showed that diverse plant viruses can multiply in fungi and vice versa. Thus, virus cross-infection between plants and fungi may play an important role in the spread, emergence, and evolution of both plant and fungal viruses and facilitate the interaction between them. In this review, we summarize current knowledge related to cross-kingdom virus infection in plants and fungi and further discuss the relevance of this new virological topic in the context of understanding virus spread and transmission in nature as well as developing control strategies for crop plant diseases.

植物和真菌之间巨大的基因和结构差异可能在一定程度上阻碍了病毒在这两个王国之间的传播。然而,最近从病毒系统发育分析和自然发生的病毒交叉感染的发现中积累的证据表明,过去和现在病毒在植物和植物相关真菌之间的传播都有发生。此外,人工病毒接种实验表明,不同的植物病毒可以在真菌中繁殖,反之亦然。因此,植物和真菌之间的病毒交叉感染可能在植物和真菌病毒的传播、出现和进化中发挥重要作用,并促进它们之间的相互作用。在这篇综述中,我们总结了目前与植物和真菌中跨界病毒感染相关的知识,并进一步讨论了这一新的病毒学主题在理解病毒在自然界中的传播和传播以及制定作物病害控制策略方面的相关性。
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引用次数: 1
Small but Highly Versatile: The Viral Accessory Protein Vpu. 小但高度通用:病毒辅助蛋白Vpu。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-07-05 DOI: 10.1146/annurev-virology-111821-100816
Meta Volcic, Lisa Wiesmüller, Frank Kirchhoff

Human and simian immunodeficiency viruses (HIVs and SIVs, respectively) encode several small proteins (Vif, Vpr, Nef, Vpu, and Vpx) that are called accessory because they are not generally required for viral replication in cell culture. However, they play complex and important roles for viral immune evasion and spread in vivo. Here, we discuss the diverse functions and the relevance of the viral protein U (Vpu) that is expressed from a bicistronic RNA during the late stage of the viral replication cycle and found only in HIV-1 and closely related SIVs. It is well established that Vpu counteracts the restriction factor tetherin, mediates degradation of the primary viral CD4 receptors, and inhibits activation of the transcription factor nuclear factor kappa B. Recent studies identified additional activities and provided new insights into the sophisticated mechanisms by which Vpu enhances and prolongs the release of fully infectious viral particles. In addition, it has been shown that Vpu prevents superinfection not only by degrading CD4 but also by modulating DNA repair mechanisms to promote degradation of nuclear viral complementary DNA in cells that are already productively infected.

人类和猴免疫缺陷病毒(分别为HIVs和SIV)编码几种小蛋白(Vif、Vpr、Nef、Vpu和Vpx),这些小蛋白被称为辅助蛋白,因为它们通常不是细胞培养中病毒复制所必需的。然而,它们在病毒免疫逃避和体内传播中发挥着复杂而重要的作用。在这里,我们讨论了病毒蛋白U(Vpu)的不同功能和相关性,该蛋白在病毒复制周期的后期由双顺反子RNA表达,仅在HIV-1和密切相关的SIV中发现。众所周知,Vpu对抗限制性因子栓系蛋白,介导原代病毒CD4受体的降解,并抑制转录因子核因子κB的激活。最近的研究确定了额外的活性,并为Vpu增强和延长完全传染性病毒颗粒释放的复杂机制提供了新的见解。此外,已经表明Vpu不仅通过降解CD4,而且通过调节DNA修复机制来防止重叠感染,以促进已经有效感染的细胞中核病毒互补DNA的降解。
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引用次数: 0
Regulation of Immune Homeostasis, Inflammation, and HIV Persistence by the Microbiome, Short-Chain Fatty Acids, and Bile Acids. 微生物组、短链脂肪酸和胆汁酸对免疫稳态、炎症和HIV持续性的调节。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 DOI: 10.1146/annurev-virology-040323-082822
Ana Beatriz Enriquez, Felipe Ten Caten, Khader Ghneim, Rafick-Pierre Sekaly, Ashish Arunkumar Sharma

Despite antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) (PLWH) continue to experience chronic inflammation and immune dysfunction, which drives the persistence of latent HIV and prevalence of clinical comorbidities. Elucidating the mechanisms that lead to suboptimal immunity is necessary for developing therapeutics that improve the quality of life of PLWH. Although previous studies have found associations between gut dysbiosis and immune dysfunction, the cellular/molecular cascades implicated in the manifestation of aberrant immune responses downstream of microbial perturbations in PLWH are incompletely understood. Recent literature has highlighted that two abundant metabolite families, short-chain fatty acids (SCFAs) and bile acids (BAs), play a crucial role in shaping immunity. These metabolites can be produced and/or modified by bacterial species that make up the gut microbiota and may serve as the causal link between changes to the gut microbiome, chronic inflammation, and immune dysfunction in PLWH. In this review, we discuss our current understanding of the role of the microbiome on HIV acquisition and latent HIV persistence despite ART. Further, we describe cellular/molecular cascades downstream of SCFAs and BAs that drive innate or adaptive immune responses responsible for promoting latent HIV persistence in PLWH. This knowledge can be used to advance HIV cure efforts.

尽管进行了抗逆转录病毒疗法(ART),但人类免疫缺陷病毒(HIV)感染者仍会经历慢性炎症和免疫功能障碍,这导致潜在HIV的持续存在和临床合并症的流行。阐明导致次优免疫的机制对于开发提高PLWH生活质量的治疗方法是必要的。尽管先前的研究已经发现肠道微生态失调和免疫功能障碍之间的联系,但与PLWH中微生物扰动下游异常免疫反应表现有关的细胞/分子级联反应尚不完全清楚。最近的文献强调,两个丰富的代谢产物家族,短链脂肪酸(SCFA)和胆汁酸(BA),在形成免疫力方面发挥着至关重要的作用。这些代谢产物可以由组成肠道微生物群的细菌产生和/或修饰,并可能成为PLWH中肠道微生物组变化、慢性炎症和免疫功能障碍之间的因果关系。在这篇综述中,我们讨论了我们目前对微生物组在HIV获得和潜在HIV持续性中的作用的理解,尽管有ART。此外,我们描述了SCFAs和BA下游的细胞/分子级联,它们驱动先天或适应性免疫反应,负责促进PLWH中潜在HIV的持续性。这些知识可用于推动艾滋病毒的治疗工作。
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引用次数: 1
Viral Evolution Shaped by Host Proteostasis Networks. 宿主蛋白质稳定网络塑造的病毒进化。
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2023-09-29 Epub Date: 2023-04-18 DOI: 10.1146/annurev-virology-100220-112120
Jimin Yoon, Jessica E Patrick, C Brandon Ogbunugafor, Matthew D Shoulders

Understanding the factors that shape viral evolution is critical for developing effective antiviral strategies, accurately predicting viral evolution, and preventing pandemics. One fundamental determinant of viral evolution is the interplay between viral protein biophysics and the host machineries that regulate protein folding and quality control. Most adaptive mutations in viruses are biophysically deleterious, resulting in a viral protein product with folding defects. In cells, protein folding is assisted by a dynamic system of chaperones and quality control processes known as the proteostasis network. Host proteostasis networks can determine the fates of viral proteins with biophysical defects, either by assisting with folding or by targeting them for degradation. In this review, we discuss and analyze new discoveries revealing that host proteostasis factors can profoundly shape the sequence space accessible to evolving viral proteins. We also discuss the many opportunities for research progress proffered by the proteostasis perspective on viral evolution and adaptation.

了解影响病毒进化的因素对于制定有效的抗病毒策略、准确预测病毒进化和预防流行病至关重要。病毒进化的一个基本决定因素是病毒蛋白质生物物理学和调节蛋白质折叠和质量控制的宿主机制之间的相互作用。病毒中的大多数适应性突变在生物物理上是有害的,导致病毒蛋白产物具有折叠缺陷。在细胞中,蛋白质折叠是由一个被称为蛋白稳定网络的伴侣蛋白和质量控制过程的动态系统辅助的。宿主蛋白稳定网络可以通过协助折叠或靶向降解来确定具有生物物理缺陷的病毒蛋白的命运。在这篇综述中,我们讨论和分析了新的发现,这些发现揭示了宿主蛋白稳定因子可以深刻地塑造进化中的病毒蛋白可进入的序列空间。我们还讨论了病毒进化和适应的蛋白稳定视角为研究进展提供的许多机会。
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引用次数: 0
The Role of Viruses in Identifying and Analyzing RNA Silencing. 病毒在鉴定和分析RNA沉默中的作用。
IF 11.3 1区 医学 Q1 VIROLOGY Pub Date : 2022-09-29 DOI: 10.1146/annurev-virology-091919-064218
David C Baulcombe

Adaptive antiviral immunity in plants is an RNA-based mechanism in which small RNAs derived from both strands of the viral RNA are guides for an Argonaute (AGO) nuclease. The primed AGO specifically targets and silences the viral RNA. In plants this system has diversified to involve mobile small interfering RNAs (siRNAs), an amplification system involving secondary siRNAs and targeting mechanisms involving DNA methylation. Most, if not all, plant viruses encode multifunctional proteins that are suppressors of RNA silencing that may also influence the innate immune system and fine-tune the virus-host interaction. Animal viruses similarly trigger RNA silencing, although it may be masked in differentiated cells by the interferon system and by the action of the virus-encoded suppressor proteins. There is huge potential for RNA silencing to combat viral disease in crops, farm animals, and people, although there are complications associated with the various strategies for siRNA delivery including transgenesis. Alternative approaches could include using breeding or small molecule treatment to enhance the inherent antiviral capacity of infected cells.

植物的适应性抗病毒免疫是一种基于RNA的机制,其中来自病毒RNA两条链的小RNA是Argonaute (AGO)核酸酶的向导。引物AGO特异性靶向并沉默病毒RNA。在植物中,这个系统已经多样化,包括可移动的小干扰rna (sirna),一个涉及次级sirna的扩增系统和涉及DNA甲基化的靶向机制。大多数(如果不是全部的话)植物病毒编码多功能蛋白,这些蛋白是RNA沉默的抑制因子,也可能影响先天免疫系统并微调病毒与宿主的相互作用。动物病毒类似地触发RNA沉默,尽管它可能在分化细胞中被干扰素系统和病毒编码抑制蛋白的作用所掩盖。RNA沉默在对抗作物、农场动物和人类的病毒性疾病方面具有巨大的潜力,尽管包括转基因在内的各种siRNA递送策略存在并发症。替代方法可能包括使用育种或小分子治疗来增强受感染细胞固有的抗病毒能力。
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引用次数: 17
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 VIROLOGY 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
期刊
Annual Review of Virology
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