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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 VIROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-30 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
Are There More Human Cancer Viruses Left to Be Found? 是否还有更多人类癌症病毒有待发现?
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2024-09-01 DOI: 10.1146/annurev-virology-111821-103721
Patrick S Moore, Yuan Chang

Of the thousands of viruses infecting humans, only seven cause cancer in the general population. Tumor sequencing is now a common cancer medicine procedure, and so it seems likely that more human cancer viruses already would have been found if they exist. Here, we review cancer characteristics that can inform a dedicated search for new cancer viruses, focusing on Kaposi sarcoma herpesvirus and Merkel cell polyomavirus as the most recent examples of successful genomic and transcriptomic searches. We emphasize the importance of epidemiology in determining which cancers to examine and describe approaches to virus discovery. Barriers to virus discovery, such as novel genomes and viral suppression of messenger RNA expression, may exist that prevent virus discovery using existing approaches. Optimally virus hunting should be performed in such a way that if no virus is found, the tumor can be reasonably excluded from having an infectious etiology and new information about the biology of the tumor can be found.

在感染人类的数千种病毒中,只有七种会导致普通人群患癌。目前,肿瘤测序已成为一种常见的癌症医学程序,因此,如果有更多的人类癌症病毒存在,很可能已经被发现。在此,我们回顾了可为专门寻找新癌症病毒提供信息的癌症特征,重点介绍了卡波西肉瘤疱疹病毒和梅克尔细胞多瘤病毒,它们是基因组和转录组搜索成功的最新范例。我们强调流行病学在确定检查哪些癌症方面的重要性,并介绍了发现病毒的方法。发现病毒的障碍可能存在,例如新基因组和病毒对信使 RNA 表达的抑制,这些障碍阻碍了利用现有方法发现病毒。最理想的病毒猎杀方式是,如果没有发现病毒,则可以合理地排除肿瘤的感染病因,并发现有关肿瘤生物学的新信息。
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引用次数: 0
Artificial Intelligence and Scientific Reviews. 人工智能与科学评论》。
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-30 DOI: 10.1146/annurev-vi-11-060624-100111
Julie K Pfeiffer, Terence S Dermody
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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 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-30 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
False Alarm: XMRV, Cancer, and Chronic Fatigue Syndrome. 虚假警报XMRV、癌症和慢性疲劳综合征。
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-30 DOI: 10.1146/annurev-virology-111821-125122
John M Coffin, Mary F Kearney

Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was first described in 2006 in some human prostate cancers. But it drew little attention until 2009, when it was also found, as infectious virus and as MLV-related DNA, in samples from people suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This discovery was rapidly followed by efforts of the international research community to understand the significance of the association and its potential to spread widely as an important human pathogen. Within a few years, efforts by researchers worldwide failed to repeat these findings, and mounting evidence for laboratory contamination with mouse-derived virus and viral DNA sequences became accepted as the explanation for the initial findings. As researchers engaged in these studies, we present here a historical review of the rise and fall of XMRV as a human pathogen, and we discuss the lessons learned from these events.

2006年,人们首次在一些人类前列腺癌中发现了与异型小鼠白血病病毒(MLV)相关的病毒(XMRV)。但直到 2009 年,在肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)患者的样本中也发现了传染性病毒和与 MLV 相关的 DNA,这才引起了人们的注意。这一发现迅速引起了国际研究界的关注,以了解这种关联的重要性及其作为一种重要人类病原体广泛传播的潜力。几年内,全球研究人员的努力都未能重复这些发现,越来越多的证据表明,小鼠源性病毒和病毒 DNA 序列造成了实验室污染,这已被公认为是对最初发现的解释。作为参与这些研究的研究人员,我们在此对 XMRV 作为人类病原体的兴衰进行了历史回顾,并讨论了从这些事件中吸取的教训。
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引用次数: 0
Diverse Antiphage Defenses Are Widespread Among Prophages and Mobile Genetic Elements. 噬菌体和移动遗传因子中普遍存在多种抗噬菌体防御机制
IF 8.1 1区 医学 Q1 VIROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-30 DOI: 10.1146/annurev-virology-100422-125123
Landon J Getz, Karen L Maxwell

Bacterial viruses known as phages rely on their hosts for replication and thus have developed an intimate partnership over evolutionary time. The survival of temperate phages, which can establish a chronic infection in which their genomes are maintained in a quiescent state known as a prophage, is tightly coupled with the survival of their bacterial hosts. As a result, prophages encode a diverse antiphage defense arsenal to protect themselves and the bacterial host in which they reside from further phage infection. Similarly, the survival and success of prophage-related elements such as phage-inducible chromosomal islands are directly tied to the survival and success of their bacterial host, and they also have been shown to encode numerous antiphage defenses. Here, we describe the current knowledge of antiphage defenses encoded by prophages and prophage-related mobile genetic elements.

被称为噬菌体的细菌病毒依赖宿主进行复制,因此在进化过程中建立了亲密的伙伴关系。温带噬菌体可以建立慢性感染,其基因组处于静止状态,称为噬菌体,噬菌体的生存与其细菌宿主的生存密切相关。因此,噬菌体编码了多种抗噬菌体防御武器,以保护自身及其所在的细菌宿主免受噬菌体的进一步感染。同样,噬菌体诱导染色体岛等噬菌体相关元件的存活和成功与其细菌宿主的存活和成功直接相关,它们也被证明编码了多种抗噬菌体防御功能。在此,我们将介绍噬菌体和噬菌体相关移动遗传元件编码的抗噬菌体防御功能的现有知识。
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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 VIROLOGY 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 VIROLOGY 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 VIROLOGY 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 VIROLOGY 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
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Annual Review of Virology
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