poxvirus

痘病毒
  • 文章类型: Journal Article
    痘病毒已经进化出一系列逃避免疫反应的机制,我们提供了不同免疫调节策略的概述。痘病毒会阻止病毒DNA的识别,从而触发免疫反应并抑制受感染细胞内的信号传导途径。痘病毒的一个独特特征是产生模拟细胞因子和细胞因子受体的分泌蛋白,充当诱饵受体以中和细胞因子和趋化因子的活性。这些蛋白质通过抑制细胞因子激活逃避细胞免疫反应的能力得到痘病毒阻断自然杀伤细胞和细胞毒性T细胞的策略的补充。通常通过干扰抗原呈递途径。靶向补体激活的机制也由痘病毒编码。靶向免疫分子和途径的病毒编码蛋白在免疫调节中起主要作用,以及它们对病毒发病机理的贡献,促进病毒复制或预防免疫病理学,正在讨论。
    Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses\' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.
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  • 文章类型: Journal Article
    一种称为猴痘病毒(MPV)的双链DNA病毒,属于Poxviridae家族和正痘病毒属,可引起猴痘病毒(mpox)感染。这种病毒过去只感染中央,东,和西非。然而,它最近已经蔓延到非洲以外的地方。MPV爆发的范围如此之高,以至于2022年7月23日,世界卫生组织(WHO)宣布这是国际关注的突发公共卫生事件(PHEIC)。大约一年后,世卫组织于2023年5月11日通知全球突发公共卫生事件结束。这里,我们旨在评估MPV引起突发公共卫生事件的当前致病性和潜在风险.
    我们从PubMed上发表的文章中搜索了信息,Scopus,和科学直接。我们用猴痘,水痘,猴痘爆发,并以猴痘病毒为关键词进行文献检索。
    许多新的MPV变种已经出现在世界各地,它们为mpox创造了PHEIC。考虑到低杀伤力和传播率,水痘不再是全球公共卫生威胁。此外,治疗和预防措施的可用性帮助医疗保健当局以有效的方式对抗水痘感染。在这次审查中,我们描绘了从过去到现在的历史和演变,以及对未来结果的看法。此外,在这篇文章中,我们已经讨论了与水痘相关的症状,并批准了抗病毒治疗策略来抵御感染。这篇综述还强调了世卫组织为患者制定的预防指南,看护者,和医疗保健提供者控制水痘感染的爆发。
    我们相信本文将向医疗当局提供有关最近多国猴痘爆发的潜在公共卫生威胁的想法,以采取相应措施。
    UNASSIGNED: A double-stranded DNA virus called monkeypox virus (MPV) belonging to the Poxviridae family and Orthopoxvirus genus causes monkeypox (mpox) infection. This virus used to infect only Central, East, and West Africa. However, it has spread to an extent outside Africa recently. The range of MPV outbreaks was so high that on July 23, 2022, the World Health Organization (WHO) declared it a Public Health Emergency of International Concern (PHEIC). About a year later, the WHO notified the end of a global public health emergency for mpox on May 11, 2023. Here, we aimed to assess the current pathogenicity and potential risk of MPV causing public health emergencies.
    UNASSIGNED: We searched information from published articles available in PubMed, Scopus, and ScienceDirect. We used monkeypox, mpox, monkeypox outbreak, and monkeypox virus as keywords during the literature search.
    UNASSIGNED: Many new variants of MPV have emerged throughout the world that created PHEIC for mpox. Considering the low lethality and transmission rate, mpox is no longer a global public health threat. In addition, the availability of therapeutic and preventive measures helped the healthcare authorities fight the mpox infection in an efficient manner. In this review, we have portrayed the history and evolution of mpox from past to present and an idea of its future outcomes. Also, we have discussed the symptoms related to mpox and approved antiviral treatment strategies to fight off the infection in this piece. This review also emphasized the preventive guidelines set by the WHO for patients, caregivers, and healthcare providers to control the outbreak of mpox infection.
    UNASSIGNED: We believe this article would give an idea about the potential public health threats of the recent multi-country monkeypox outbreak to the healthcare authorities for taking measures accordingly.
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  • 文章类型: Journal Article
    历史上,生物制剂已被用于靶向各种群体。最早的例子之一可能是18世纪澳大利亚天花的灾难性影响(正如一些历史学家所说的那样)。现代生物技术可用于创建或提供针对各种生物战剂的保护。任何微生物(病毒,细菌,和真菌)或其毒素可用作生物制剂。明尼苏达州卫生部已将天花(天花)列为A类生物恐怖主义剂,尽管它在1980年通过广泛的疫苗接种运动被根除。A类试剂被认为是对公共卫生的最高风险。与实验室相关的痘病毒爆发可能会造成前所未有的职业危害。美国和俄罗斯只有两个世卫组织批准的BSL-4设施被允许进行天花病毒研究。所以,痘病毒表现为双重用途困境的经典案例,因为对它们的研究可以用于有益和有害的目的。尽管伦理学在科学研究中的重要性不需要进一步阐述,伦理规范在痘病毒实验中具有更大的意义。在这一章中,我们将向读者介绍进行痘病毒研究的敏感性,以及这些病毒如何成为潜在生物武器的来源。最后,探索指定的道德准则,以确保安全的病毒学研究实践。
    Historically, biological agents have been used to target various populations. One of the earliest examples could be the catastrophic effect of smallpox in Australia in the eighteenth century (as alleged by some historians). Modern biological techniques can be used to both create or provide protection against various agents of biological warfare. Any microorganism (viruses, bacteria, and fungi) or its toxins can be used as biological agents. Minnesota Department of Health has listed Smallpox (variola major) as a category A bioterrorism agent, even though it has been eradicated in 1980 through an extensive vaccination campaign. Category A agents are considered the highest risk to public health. Laboratory-associated outbreaks of poxviruses could cause unprecedented occupational hazards. Only two WHO-approved BSL-4 facilities in the United States and Russia are allowed to perform research on the variola virus. So, poxviruses present themselves as a classical case of a dual-use dilemma, since research with them can be used for both beneficial and harmful purposes. Although the importance of ethics in scientific research requires no further elaboration, ethical norms assume greater significance during experimentation with poxviruses. In this chapter, we will update the readers on the sensitive nature of conducting research with poxviruses, and how these viruses can be a source of potential biological weapons. Finally, specified ethical guidelines are explored to ensure safe research practices in virology.
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  • 文章类型: Journal Article
    猴痘在刚果和尼日利亚流行至少五十年。自2022年5月初以来,世界各地发生了许多前所未有的疫情,此前没有任何病例报告。虽然大多数确诊病例在欧洲和美洲,一些病例发生在非地方性非洲国家。截至2022年12月,全球已报告82,999例引起世界卫生组织(世卫组织)成员的关注。虽然世卫组织尚未将这一流行病列为全球卫生紧急情况,成员国已经开始提出计划,以巩固其紧急疫苗库存,并分享由单一FDA批准的制造商生产的有限数量的疫苗,巴伐利亚北欧。许多国家担心疫苗将如何共享。一些较大的捐助国被定位为疫苗共享的最大受益者,虽然自1970年代以来一直感染该病毒的地区的国家没有得到任何分配。这种疫苗分布模式与COVID-19大流行早期的情况相呼应。由于猴痘和天花的相似性,接触预防措施和疫苗接种似乎是防止其迅速传播的有效策略。我们的目标是评估类似于天花的根除程序模型如何应用于Monkeypox,以及它是否可以解决疫苗不平等问题。要做到这一点,我们使用多管齐下的方法来针对疾病监测,疫苗意识,制造,成本,和分销策略。
    Monkeypox has been endemic in Congo and Nigeria for at least five decades. Since early May 2022, there have been numerous unprecedented outbreaks throughout the world in places without any previously reported cases. While a majority of the diagnosed cases have been within Europe and the Americas, several cases have occurred in non-endemic African countries. As of December 2022, 82,999 cases had been reported globally, prompting concern among the World Health Organization (WHO) members. While the WHO has not labeled this epidemic a Global Health Emergency, member states have begun to put forward plans to consolidate their emergency vaccine stockpiles and share the limited number of vaccines made by the single FDA-approved manufacturer, Bavarian Nordic. Many countries are concerned about how vaccines will be shared. Some of the larger donor States are positioned to be the biggest beneficiaries of vaccine sharing, while States from areas that have been suffering from the virus since the 1970s have not been allocated any. This pattern of vaccine distribution echoes that seen during the early part of the COVID-19 pandemic. Due to the similarities between Monkeypox and Smallpox, contact precautions and vaccination seem to be effective strategies to combat its rapid spread. We aim to evaluate how an eradication program model similar to that used for Smallpox can be applied to Monkeypox, and whether it can address vaccine inequity. To do this, we use a multi-pronged approach targeting disease surveillance, vaccine awareness, manufacturing, cost, and distribution strategies.
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  • 文章类型: Journal Article
    几十年来,痘病毒组装一直是一个有趣的研究领域。虽然实验技术的进步不断产生新的见解,许多问题仍未解决。基因组大小达380kbp,非对称结构,外部脂质双层,细胞质生命周期是这些病毒的一些显著特征。颗粒内部是两个侧体和包含病毒核衣壳的蛋白质壁结合的双凹核心。组装通过五个主要阶段-内质网(ER)膜改变和破裂,新月形成,未成熟的病毒体形成,基因组衣壳化,病毒体成熟和一部分病毒,病毒体在传播之前的额外包裹。已显示几种大型dsDNA病毒遵循可比较的事件序列。在这一章中,我们回顾了我们对痘病毒形态发生过程的理解,同时回顾了该领域的最新进展。我们还简要讨论了病毒体组装如何帮助我们了解痘病毒和其他核质大DNA病毒(NCLDVs)之间的进化联系。
    Poxvirus assembly has been an intriguing area of research for several decades. While advancements in experimental techniques continue to yield fresh insights, many questions are still unresolved. Large genome sizes of up to 380 kbp, asymmetrical structure, an exterior lipid bilayer, and a cytoplasmic life cycle are some notable characteristics of these viruses. Inside the particle are two lateral bodies and a protein wall-bound-biconcave core containing the viral nucleocapsid. The assembly progresses through five major stages-endoplasmic reticulum (ER) membrane alteration and rupture, crescent formation, immature virion formation, genome encapsidation, virion maturation and in a subset of viruses, additional envelopment of the virion prior to its dissemination. Several large dsDNA viruses have been shown to follow a comparable sequence of events. In this chapter, we recapitulate our understanding of the poxvirus morphogenesis process while reviewing the most recent advances in the field. We also briefly discuss how virion assembly aids in our knowledge of the evolutionary links between poxviruses and other Nucleocytoplasmic Large DNA Viruses (NCLDVs).
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  • 文章类型: Journal Article
    在过去的4年里,世界经历了两次蝙蝠传播病毒的大流行。首先,2019年,SARS-CoV-2大流行开始,并在世界各地造成数百万人死亡。2022年,世界各国爆发了猴痘大流行。这些流行病见证了医疗保健和研究机构的运动和倡议,以建立全球认识,以应对任何未来的流行病和生物威胁。一个健康概念是现代的,全面,统一改善人类的方法,动物,和生态系统健康。这个概念显示了它们是多么的相互交织和相互关联,无论是环境,或病理关系。这篇综述旨在描述Poxviridae及其对一种健康概念的影响,通过研究痘病毒如何影响动物健康的根本原因,人类,和环境。回顾疾病在动物与人类之间传播的影响,人类对人类,并将动物与痘病毒作为第三方,以实现对感染和病毒传播的全面了解。因此,有助于增强检测,诊断,研究,以及关于OneHealth应用的治疗方法。
    In the last 4 years, the world has experienced two pandemics of bat-borne viruses. Firstly, in 2019 the SARS-CoV-2 pandemic started and has been causing millions of deaths around the world. In 2022, a Monkeypox pandemic rose in various countries of the world. Those pandemics have witnessed movements and initiatives from healthcare and research institutions to establish a worldwide understanding to battle any future pandemics and biological threats. One Health concept is a modern, comprehensive, unifying ways to improve humans, animals, and ecosystems\' health. This concept shows how much they are intertwined and related to one another, whether it is an environmental, or a pathological relation. This review aims to describe Poxviridae and its impact on the One Health concept, by studying the underlying causes of how poxviruses can affect the health of animals, humans, and environments. Reviewing the effect of disease transmission between animal to human, human to human, and animal to animal with pox viruses as a third party to achieve a total understanding of infection and viral transmission. Thus, contributing to enhance detection, diagnosis, research, and treatments regarding the application of One Health.
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  • 文章类型: Journal Article
    病毒载体疫苗代表了免疫技术的重大进步,与传统疫苗模式相比,提供了许多好处。由于其独特的属性,Orf病毒(ORFV)株D1701-VrV是疫苗开发的特别有前途的候选者,例如良好的安全性,引起体液和细胞免疫的能力,及其良好的遗传和热稳定性。尽管ORFV的理论安全优势,例如其宿主范围狭窄和接种后系统传播有限,这些理论获益与关于其体内安全性的经验证据之间仍然存在关键差距.这种差异强调了需要全面的临床前验证来弥合这一知识差距,特别是考虑到ORFV在人类中的使用。我们的研究引入了Prime-2-CoV,一种针对COVID-19的基于ORFV的创新候选疫苗,旨在通过表达SARS-CoV-2核衣壳和Spike蛋白引发强大的免疫反应。目前正在进行临床试验,Prime-2-CoV标志着ORFV在人类受试者中的首次应用。解决上述安全问题,我们广泛的临床前评估,包括对大鼠和免疫受损NOG小鼠的环境风险评估(ERA)和详细的药代动力学研究,显示Prime-2-CoV的有利药代动力学特征,可忽略的环境影响,和最小的ERA风险。这些发现不仅肯定了疫苗的安全性和有效性,而且开创了使用基于ORFV的疗法,突出了其更广泛的治疗应用的潜力。
    Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV\'s theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile. This discrepancy underscores the need for comprehensive preclinical validations to bridge this knowledge gap, especially considering ORFV\'s use in humans. Our research introduces Prime-2-CoV, an innovative ORFV-based vaccine candidate against COVID-19, designed to elicit a robust immune response by expressing SARS-CoV-2 Nucleocapsid and Spike proteins. Currently under clinical trials, Prime-2-CoV marks the inaugural application of ORFV in human subjects. Addressing the aforementioned safety concerns, our extensive preclinical evaluation, including an environmental risk assessment (ERA) and detailed pharmacokinetic studies in rats and immunocompromised NOG mice, demonstrates Prime-2-CoV\'s favorable pharmacokinetic profile, negligible environmental impact, and minimal ERA risks. These findings not only affirm the vaccine\'s safety and efficacy but also pioneer the use of ORFV-based therapeutics, highlighting its potential for wider therapeutic applications.
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  • 文章类型: Journal Article
    皮肤是一种复杂的组织,它提供了强大的物理屏障来抵抗病原体的入侵。尽管如此,许多病毒可以进入皮肤,并在表皮角质形成细胞或真皮免疫细胞中成功复制。在这次审查中,我们提供了对皮肤病毒感染的抗病毒T细胞生物学反应的概述,以及这些反应如何根据感染的细胞靶标而有所不同。我们对皮肤感染的T细胞监测的许多机制理解已经从痘病毒和疱疹病毒感染的小鼠模型中获得。然而,我们还讨论了其他病毒感染,包括黄病毒和乳头瘤病毒,其中对皮肤T细胞反应的研究较少。除了成功的T细胞控制皮肤病毒感染的机制,我们强调知识差距和未来可能对人类健康产生影响的方向。
    The skin is a complex tissue that provides a strong physical barrier against invading pathogens. Despite this, many viruses can access the skin and successfully replicate in either the epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of the antiviral T cell biology responding to cutaneous viral infections and how these responses differ depending on the cellular targets of infection. Much of our mechanistic understanding of T cell surveillance of cutaneous infection has been gained from murine models of poxvirus and herpesvirus infection. However, we also discuss other viral infections, including flaviviruses and papillomaviruses, in which the cutaneous T cell response has been less extensively studied. In addition to the mechanisms of successful T cell control of cutaneous viral infection, we highlight knowledge gaps and future directions with possible impact on human health.
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  • 文章类型: Preprint
    这项研究的最初目的是通过分析公开可用的深度测序数据集的从头组装来阐明小DNA肿瘤病毒的进化。该调查生成了一个可搜索的重叠群快照数据库,代表100,000多个序列读取存档记录。使用现代结构感知搜索工具,我们反复扩大搜索范围,以包括越来越广泛的其他病毒家族。分析揭示了令人惊讶的不同范围的嵌合体,涉及不同的病毒组。在某些情况下,类似于已知DNA复制模块或已知病毒体蛋白操纵子的基因与无法识别的序列配对,结构预测表明这些序列可能代表以前未知的复制酶和新型病毒体结构。在代表人类和其他灵长类动物的数据集中发现了一个新兴群体的离散进化枝,称为腺体病毒。作为概念的证明,我们表明,重叠群数据库也可用于发现RNA病毒和候选古细菌噬菌体。辅助搜索揭示了不同病毒组之间嵌合的其他实例。这些观察结果支持以基因为中心的分类学框架,该框架应该对未来的病毒狩猎工作有用。
    The initial objective of this study was to shed light on the evolution of small DNA tumor viruses by analyzing de novo assemblies of publicly available deep sequencing datasets. The survey generated a searchable database of contig snapshots representing more than 100,000 Sequence Read Archive records. Using modern structure-aware search tools, we iteratively broadened the search to include an increasingly wide range of other virus families. The analysis revealed a surprisingly diverse range of chimeras involving different virus groups. In some instances, genes resembling known DNA-replication modules or known virion protein operons were paired with unrecognizable sequences that structural predictions suggest may represent previously unknown replicases and novel virion architectures. Discrete clades of an emerging group called adintoviruses were discovered in datasets representing humans and other primates. As a proof of concept, we show that the contig database is also useful for discovering RNA viruses and candidate archaeal phages. The ancillary searches revealed additional examples of chimerization between different virus groups. The observations support a gene-centric taxonomic framework that should be useful for future virus-hunting efforts.
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  • 文章类型: Journal Article
    块状皮肤病病毒(LSDV)是Poxviridae家族的羊痘病毒(CPPV)属的成员。LSDV是一种迅速崛起的,牛的高后果病原体,最近从非洲和中东蔓延到欧洲和亚洲。我们已经对Pirbright研究所病毒档案中的历史LSDV分离株的全基因组进行了测序,以及斯里兰卡最近爆发的疾病的现场分离株,蒙古,尼日利亚和埃塞俄比亚。将这些基因组序列与已发表的基因组进行比较,并分为不同的亚组。两个亚组包含疫苗或疫苗样样本(“Neethling样”进化枝1.1和“Kenya样”亚组,进化枝1.2.2)。一个亚组与中东/欧洲的LSD暴发有关(进化枝1.2.1),一个以前未报告的亚组起源于西非和中非的LSD病例(进化枝1.2.3)。还鉴定了包含来自野生型和疫苗样品(疫苗样重组体,分组为进化枝2)。从非洲不同地区分离的LSDV菌株的全基因组测序和分析,欧洲和亚洲提供了有关LSDV出现的驱动因素的新知识,并将为未来的疾病控制策略提供信息。
    Lumpy skin disease virus (LSDV) is a member of the capripoxvirus (CPPV) genus of the Poxviridae family. LSDV is a rapidly emerging, high-consequence pathogen of cattle, recently spreading from Africa and the Middle East into Europe and Asia. We have sequenced the whole genome of historical LSDV isolates from the Pirbright Institute virus archive, and field isolates from recent disease outbreaks in Sri Lanka, Mongolia, Nigeria and Ethiopia. These genome sequences were compared to published genomes and classified into different subgroups. Two subgroups contained vaccine or vaccine-like samples (\"Neethling-like\" clade 1.1 and \"Kenya-like\" subgroup, clade 1.2.2). One subgroup was associated with outbreaks of LSD in the Middle East/Europe (clade 1.2.1) and a previously unreported subgroup originated from cases of LSD in west and central Africa (clade 1.2.3). Isolates were also identified that contained a mix of genes from both wildtype and vaccine samples (vaccine-like recombinants, grouped in clade 2). Whole genome sequencing and analysis of LSDV strains isolated from different regions of Africa, Europe and Asia have provided new knowledge of the drivers of LSDV emergence, and will inform future disease control strategies.
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