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Barriers to hepatitis C virus infection in mice 小鼠对丙型肝炎病毒感染的屏障
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.coviro.2022.101273
Michael P Schwoerer, Alexander Ploss

Hepatitis C virus (HCV) is unable to infect mice, a fact that has severely limited their use as small-animal models for HCV pathogenesis and as tools for HCV vaccine development. HCV is blocked at various stages of its life cycle in mouse cells, due to incompatibility with host factors, the presence of dominant restriction factors, and effective immune responses. Molecular mechanisms for several such blocks have been characterized. The stepwise understanding of these limitations in mice will enable the development of an immunocompetent mouse that can fully support HCV infection and exhibit disease similar to that of infected humans.

丙型肝炎病毒(HCV)不能感染小鼠,这一事实严重限制了它们作为HCV发病机制的小动物模型和HCV疫苗开发工具的使用。HCV在小鼠细胞生命周期的各个阶段都被阻断,原因是与宿主因子不相容,存在显性限制因子,以及有效的免疫应答。几个这样的块的分子机制已经被表征。逐步了解小鼠的这些局限性将有助于开发具有免疫能力的小鼠,使其能够完全支持HCV感染并表现出与受感染的人相似的疾病。
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引用次数: 1
Therapeutic approaches to Epstein–Barr virus cancers eb病毒癌的治疗方法
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.coviro.2022.101260
Samantha S Soldan, Troy E Messick, Paul M Lieberman

Epstein–Barr virus (EBV) establishes a lifelong latent infection that can be a causal agent for a diverse spectrum of cancers and autoimmune disease. A complex and dynamic viral lifecycle evades eradication by the host immune system and confounds antiviral therapeutic strategies. To date, there are no clinically approved vaccines or therapies that selectively target EBV as the underlying cause of EBV-associated disease. Here, we review the challenges and recent advances in the development of EBV-specific therapeutics for treatment of EBV-associated cancers.

eb病毒(EBV)是一种终身潜伏感染,可能是多种癌症和自身免疫性疾病的致病因子。复杂而动态的病毒生命周期逃避了宿主免疫系统的根除,并混淆了抗病毒治疗策略。迄今为止,还没有临床批准的疫苗或疗法选择性地靶向EBV作为EBV相关疾病的潜在原因。在这里,我们回顾了ebv特异性治疗治疗ebv相关癌症的挑战和最新进展。
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引用次数: 6
Druggable host gene dependencies in primary effusion lymphoma 原发性积液性淋巴瘤的可用药宿主基因依赖性
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.coviro.2022.101270
Neil Kuehnle, Eva Gottwein

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). Here, we review what is known about human gene essentiality in PEL-derived cell lines. We provide an updated list of PEL-specific human gene dependencies, based on the improved definition of core essential genes across human cancer types. The requirements of PEL cell lines for interferon regulatory factor 4 (IRF4), basic leukine zipper ATF-like transcription factor (BATF), G1/S cyclin D2 (CCND2), CASP8 and FADD like apoptosis regulator (CFLAR), MCL1 apoptosis regulator (MCL1), and murine double minute 2 (MDM2) have been confirmed experimentally. KSHV co-opts IRF4 and BATF to drive superenhancer (SE)-mediated expression of IRF4 itself, MYC, and CCND2. IRF4 dependency of SE-mediated gene expression is shared with Epstein–Barr virus-transformed lymphoblastoid cell lines (LCLs) and human T-cell leukemia virus type 1-transformed adult T-cell leukemia/lymphoma (ATLL) cell lines, as well as several B-cell lymphomas of nonviral etiology. LCLs and ATLL cell lines similarly share dependencies on CCND2 and CFLAR with PEL, but also have distinct gene dependencies. Genetic dependencies could be exploited for therapeutic intervention in PEL and other cancers.

卡波西肉瘤相关疱疹病毒(KSHV)引起原发性积液性淋巴瘤(PEL)。在这里,我们回顾了人类基因在pel衍生细胞系中的重要性。我们基于改进的人类癌症类型核心必需基因的定义,提供了一个更新的pel特异性人类基因依赖列表。PEL细胞系对干扰素调节因子4 (IRF4)、碱性白细胞拉环atf样转录因子(BATF)、G1/S周期蛋白D2 (CCND2)、CASP8和FADD样细胞凋亡调节剂(CFLAR)、MCL1细胞凋亡调节剂(MCL1)和小鼠双分钟2 (MDM2)的需求已被实验证实。KSHV选择IRF4和BATF来驱动超增强子(SE)介导的IRF4自身、MYC和CCND2的表达。Epstein-Barr病毒转化的淋巴母细胞样细胞系(LCLs)和人t细胞白血病病毒1型转化的成人t细胞白血病/淋巴瘤(ATLL)细胞系以及几种非病毒病因的b细胞淋巴瘤都具有IRF4对se介导的基因表达的依赖性。lcl和ATLL细胞系与PEL相似地共享对CCND2和CFLAR的依赖,但也具有不同的基因依赖性。遗传依赖性可用于前列腺癌和其他癌症的治疗干预。
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引用次数: 1
Gut virome in early life: origins and implications 早期生命中的肠道病毒:起源和意义
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101233
Elizabeth A Kennedy , Lori R Holtz

The human body is colonized by a multitude of bacteria, fungi, and viruses, which play important roles in health and disease. Microbial colonization during early life is thought to be a particularly important period with lasting consequences for health. Viral populations in the gut are particularly dynamic in early life before they stabilize in adulthood. The composition of the early-life virome is increasingly recognized as a determinant of disease later in life. Here, we review the development of the virome in healthy infants, as well as the role of the early-life virome in the development of disease states including diarrhea, malnutrition, and autoimmune diseases.

人体内有大量的细菌、真菌和病毒,它们在健康和疾病中起着重要的作用。生命早期的微生物定植被认为是一个特别重要的时期,对健康有持久的影响。在成年后稳定下来之前,肠道中的病毒种群在生命早期尤其活跃。生命早期病毒组的组成越来越被认为是生命后期疾病的决定因素。在这里,我们回顾了病毒体在健康婴儿中的发展,以及早期生命病毒体在疾病状态发展中的作用,包括腹泻、营养不良和自身免疫性疾病。
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引用次数: 5
Bacteriophage T4 as a nanovehicle for delivery of genes and therapeutics into human cells T4噬菌体作为一种纳米载体,将基因和治疗药物输送到人体细胞中
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101255
Venigalla B Rao, Jingen Zhu

The ability to deliver therapeutic genes and biomolecules into a human cell and restore a defective function has been the holy grail of medicine. Adeno-associated viruses and lentiviruses have been extensively used as delivery vehicles, but their capacity is limited to one (or two) gene(s). Bacteriophages are emerging as novel vehicles for gene therapy. The large 120 × 86-nm T4 capsid allows engineering of both its surface and its interior to incorporate combinations of DNAs, RNAs, proteins, and their complexes. In vitro assembly using purified components allows customization for various applications and for individualized therapies. Its large capacity, cell-targeting capability, safety, and inexpensive manufacturing could open unprecedented new possibilities for gene, cancer, and stem cell therapies. However, efficient entry into primary human cells and intracellular trafficking are significant barriers that must be overcome by gene engineering and evolution in order to translate phage-delivery technology from bench to bedside.

将治疗基因和生物分子输送到人体细胞中并恢复有缺陷的功能一直是医学界的圣杯。腺相关病毒和慢病毒已被广泛用作运载工具,但它们的能力仅限于一个(或两个)基因。噬菌体正在成为基因治疗的新型载体。巨大的120 × 86纳米T4衣壳允许对其表面和内部进行工程设计,以结合dna, rna,蛋白质及其复合物的组合。体外组装使用纯化组件允许定制各种应用和个性化治疗。它的大容量,细胞靶向能力,安全性和廉价的制造可以为基因,癌症和干细胞治疗开辟前所未有的新可能性。然而,有效进入原代人类细胞和细胞内运输是基因工程和进化必须克服的重大障碍,以便将噬菌体传递技术从实验室转化为临床。
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引用次数: 4
Viral–host interactions during splicing and nuclear export of influenza virus mRNAs 流感病毒mrna剪接和核输出过程中病毒与宿主的相互作用
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101254
Matthew Esparza, Prasanna Bhat, Beatriz MA Fontoura

As influenza-A viruses (IAV) replicate in the host cell nucleus, intranuclear pathways are usurped for viral gene expression. The eight genomic viral ribonucleoproteins (vRNPs) segments of IAV are transcribed and two generate viral mRNAs (M and NS) that undergo alternative splicing followed by export from the nucleus. The focus of this review is on viral RNA splicing and nuclear export. Recent mechanistic advances on M and NS splicing show differential regulation by RNA-binding proteins as well as distinct intranuclear localization. After a review of IAV splicing, we will discuss the nuclear export of viral mRNAs, which occur by interacting with specific constituents of the host mRNA export machinery that translocate viral mRNAs through the nuclear pore complex for translation in the cytoplasm.

当流感a- a病毒(IAV)在宿主细胞核中复制时,病毒基因表达的核内途径被篡夺。IAV的8个基因组病毒核糖核蛋白(vRNPs)片段被转录,其中两个片段产生病毒mrna (M和NS),它们经过选择性剪接,然后从细胞核输出。本文就病毒RNA剪接与核输出进行综述。最近关于M和NS剪接的机制进展表明,它们受到rna结合蛋白的不同调控以及不同的核内定位。在回顾了IAV剪接之后,我们将讨论病毒mRNA的核输出,这是通过与宿主mRNA输出机制的特定成分相互作用而发生的,宿主mRNA输出机制通过核孔复合物将病毒mRNA转运到细胞质中进行翻译。
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引用次数: 7
The enigmatic roles of Anelloviridae and Redondoviridae in humans 无绒病毒科和红多病毒科在人类中的神秘作用
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101248
Louis J Taylor , Emma L Keeler , Frederic D Bushman , Ronald G Collman

Anelloviridae and Redondoviridae are virus families with small, circular, single-stranded DNA genomes that are common components of the human virome. Despite their small genome size of less than 5000 bases, they are remarkably successful — anelloviruses colonize over 90% of adult humans, while the recently discovered redondoviruses have been found at up to 80% prevalence in some populations. Anelloviruses are present in blood and many organs, while redondoviruses are found mainly in the ororespiratory tract. Despite their high prevalence, little is known about their biology or pathogenic potential. In this review, we discuss anelloviruses and redondoviruses and explore their enigmatic roles in human health and disease.

无球病毒科和红多病毒科是具有小的环状单链DNA基因组的病毒科,是人类病毒组的常见组成部分。尽管它们的基因组很小,只有不到5000个碱基,但它们却非常成功——在90%以上的成年人中,蛔虫病毒是定植的,而最近发现的红多囊病毒在某些人群中的流行率高达80%。蛔虫病毒存在于血液和许多器官中,而虹膜病毒主要存在于呼吸道中。尽管其发病率很高,但对其生物学或致病潜力知之甚少。在这篇综述中,我们讨论了棘球病毒和红粒病毒,并探讨了它们在人类健康和疾病中的神秘作用。
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引用次数: 10
Editorial overview: Viral pathogenesis 编辑概述:病毒的发病机制
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101253
Antonio Bertoletti , Matteo Iannacone
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引用次数: 0
Editorial overview: Anti-viral strategies: Human antibody immune response and antibody-based therapy against viruses 编辑概述:抗病毒策略:人类抗体免疫反应和基于抗体的病毒治疗
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101247
Qiao Wang, Zhong Huang
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引用次数: 0
Lying low-chromatin insulation in persistent DNA virus infection 持续性DNA病毒感染中的低染色质绝缘
IF 5.9 2区 医学 Q1 VIROLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.coviro.2022.101257
Christy S Varghese, Joanna L Parish, Jack Ferguson

Persistent virus infections are achieved when the intricate balance of virus replication, host-cell division and successful immune evasion is met. The genomes of persistent DNA viruses are either maintained as extrachromosomal episomes or can integrate into the host genome. Common to both these strategies of persistence is the chromatinisation of viral DNA by cellular histones which, like host DNA, are subject to epigenetic modification. Epigenetic repression of viral genes required for lytic replication occurs, while genes required for latent or persistent infection are maintained in an active chromatin state. Viruses utilise host-cell chromatin insulators, which function to maintain epigenetic boundaries and enforce this strict transcriptional programme. Here, we review insulator protein function in virus transcription control, focussing on CCCTC-binding factor (CTCF) and cofactors. We describe CTCF-dependent activities in virus transcription regulation through epigenetic and promoter–enhancer insulation, three-dimensional chromatin looping and manipulation of transcript splicing.

当病毒复制、宿主细胞分裂和成功的免疫逃避达到复杂的平衡时,才能实现持续的病毒感染。持久性DNA病毒的基因组要么作为染色体外片段维持,要么可以整合到宿主基因组中。这两种持久性策略的共同之处是细胞组蛋白对病毒DNA的染色质化,与宿主DNA一样,细胞组蛋白也会受到表观遗传修饰。裂解复制所需的病毒基因发生表观遗传抑制,而潜伏或持续感染所需的基因维持在活性染色质状态。病毒利用宿主细胞染色质绝缘体,其功能是维持表观遗传边界并执行这种严格的转录程序。本文综述了绝缘子蛋白在病毒转录控制中的功能,重点介绍了ccctc结合因子(CTCF)和辅助因子。我们通过表观遗传和启动子-增强子绝缘、三维染色质环和转录剪接操作描述了病毒转录调控中ctcf依赖的活性。
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引用次数: 2
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Current opinion in virology
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