orthopoxvirus

正痘病毒
  • 文章类型: Journal Article
    猴痘(MPX),一种非洲流行的正痘病毒病,现在是世界卫生组织于2023年7月宣布的国际关注的公共卫生紧急情况(PHEIC)。虽然一般是温和的,据报道,总病死率为3%,在与男性发生性关系的男性中,基本繁殖数(R0)>1(MSM,即,葡萄牙(1.4),联合王国(1.6),西班牙(1.8)。然而,在其他设置中,R0<1。与天花病毒一致,预计这也会增加母亲和胎儿出现不良后果的风险.这种疾病在免疫受损的妊娠状态下的结果是可怕的,显示母亲和胎儿的高死亡率和发病率,胎儿副作用的风险高达75%,严重孕产妇疾病的风险高达25%。因此,它需要及时诊断和干预。逆转录聚合酶链反应(RTPCR)测试是诊断的标准方法。我们总结了MPX对妊娠的最新发现,以及相关的危险因素。我们还给出了积极监测胎儿的建议,围产期保健,和良好的报告,以改善结果。可用的疫苗已显示出预防初级疾病的希望。
    Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention.
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  • 文章类型: Journal Article
    在2023年夏季,欧洲地区经历了在2022年大规模爆发后,水痘病例的数量有限。这种增加的特征是异步和双峰增加,国家在不同的时间经历高峰。复苏期间病例的人口统计学特征与以前报告的情况基本一致。来自欧洲区域的所有可用序列都属于IIb进化枝。持续的努力对于控制并最终消除欧洲地区的水痘至关重要。
    During the summer of 2023, the European Region experienced a limited resurgence of mpox cases following the substantial outbreak in 2022. This increase was characterised by asynchronous and bimodal increases, with countries experiencing peaks at different times. The demographic profile of cases during the resurgence was largely consistent with those reported previously. All available sequences from the European Region belonged to clade IIb. Sustained efforts are crucial to control and eventually eliminate mpox in the European Region.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    Poxviridae的正痘病毒(OPXV)属包括人类病原体天花病毒(VARV),猴痘病毒(MPXV),痘苗病毒(VACV),和一些人畜共患病毒。VACV的许多Bcl-2样蛋白参与逃避宿主先天免疫。然而,在其他OPXVs中,很少有工作致力于其直系同源物的进化和功能。这里,我们发现由P2L基因编码的MPXV蛋白P2,和来自其他OPXV的P2直系同源物,例如VACV蛋白N2,定位于细胞核并拮抗干扰素(IFN)的产生。例外的是缺少核定位信号(NLS)的骆驼痘病毒(CMLV)和taterapox病毒(TATV)中的截短的P2直向同源物。机械上,MPXVP2的NLS与核蛋白α-2(KPNA2)相互作用以促进P2核易位,并竞争性抑制KPNA2介导的IRF3核易位和下游IFN的产生。在P2或直系同源物中NLS的缺失显着增强IRF3核易位和先天免疫反应,从而减少病毒复制。此外,在VACV中从N2中缺失NLS减弱了小鼠中的病毒复制和毒力。这些数据表明,NLS介导的P2易位对于P2诱导的先天免疫抑制至关重要。我们的发现有助于深入了解OPXVP2直向同源物在先天免疫逃避中的机制。
    The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.
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  • 文章类型: Journal Article
    目的:强调以眼部表现为重点的痘的临床特征,并回顾这种重新出现的感染性疾病的治疗方案。
    结果:眼痘受累因进化枝而异。与以前的爆发相比,最近的2022年爆发似乎与结膜炎病例减少有关。然而,在这个新出现的进化枝期间发生的眼部发现可能具有视觉威胁,包括角膜炎的病例,进展迅速的巩膜炎,坏死性眶周皮疹.
    结论:眼部痘病毒是全身性痘病毒(MPXV)感染的重要临床特征。加强临床怀疑允许及时诊断和开始抗病毒治疗,在适当的时候。缺乏关于水痘全身和眼部治疗疗效的随机临床试验。天花和体外水痘数据的先前临床经验支持全身抗病毒药物的使用,如tecovirimat,西多福韦,在眼痘管理中,布列丁福韦和氟尿苷的局部使用,尽管可以发生耐药感染,并预示预后不良。
    OBJECTIVE: To highlight the clinical features of mpox with an emphasis on ocular manifestations and to review treatment options for this re-emerging infectious disease.
    RESULTS: Ocular involvement of mpox varies by clade. The most recent 2022 outbreak appears to be associated with fewer conjunctivitis cases compared to previous outbreaks. However, the ocular findings occurring during this newly emerging clade can be visually threatening and include cases of keratitis, rapidly progressing scleritis, and necrotizing periorbital rashes.
    CONCLUSIONS: Ocular mpox is an important clinical feature of systemic mpox virus (MPXV) infection. Heightened clinical suspicion allows for a timely diagnosis and the initiation of antiviral treatment, when appropriate. Randomized clinical trials for mpox systemic and ocular treatment efficacy are lacking. Prior clinical experience with smallpox and in-vitro mpox data support the use of systemic antivirals such as tecovirimat, cidofovir, brincidofovir and topical use of trifluridine in ocular mpox management, though treatment-resistant infection can occur and portend a poor prognosis.
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  • 文章类型: Journal Article
    2022年,就在COVID-19大流行结束之前,许多国家注意到病毒性猴痘的爆发。猴痘病毒,一种人畜共患病原体,导致人类高热疾病,类似天花。预防策略包括疫苗接种,严格的感染控制措施,避免与感染者接触。随着猴痘和相关痘病毒继续构成挑战,持续监视,早期诊断,迅速隔离,有效的控制措施对于限制传播和减轻疫情对公共卫生的影响至关重要。这篇综述为猴痘病毒的进化及其各种传播方式提供了宝贵的见解,包括死后传播,并对印度政府发布的预防和有效控制这种疾病传播的指导方针提供了总体看法。
    In 2022, just before the COVID-19 pandemic ended, many countries noticed a viral monkeypox outbreak. Monkeypox virus, a zoonotic pathogen, causes a febrile illness in humans and resembles smallpox. Prevention strategies encompass vaccination, strict infection control measures, and avoiding contact with infected persons. As monkeypox and related poxviruses continue to pose challenges, ongoing surveillance, early diagnosis, prompt isolation, and effective control measures are crucial for limiting transmission and mitigating the impact of outbreaks on public health. This review provides valuable insights into the evolution of the monkeypox virus and its various modes of transmission, including postmortem transmission, and offers an overall perspective on the guidelines issued by the Government of India to prevent and effectively control the spread of this disease.
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  • 文章类型: Journal Article
    最近爆发的水痘疫情,由猴痘病毒(MPXV)引起,对全球公共卫生构成了新的威胁。这里,我们最初评估了免疫计划结束前出生的牛痘疫苗中MPXVB6蛋白的预先存在的抗体水平,然后鉴定了两种单克隆抗体(MAb),hMB621和hMB668,靶向B6上的不同表位,来自一名疫苗。结合测定表明,两种单克隆抗体在牛痘(VACV)中对B6及其直系同源物表现出广泛的结合能力,天花(VARV)和牛痘病毒(CPXV)。中和测定显示,两种MAb显示针对VACV的有效中和。使用BALB/c雌性小鼠模型的动物实验表明,两种MAb通过腹膜内注射显示出针对VACV的有效保护。此外,我们确定了B6和hMB668的复合结构,揭示了B6的结构特征和hMB668的表位。总的来说,我们的研究提供了两种有希望的候选抗体,用于治疗正痘病毒感染,包括水痘.
    The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.
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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
    流行病学研究已经确定,由于CladeIIb痘病毒(MPXV),2022-2023年在全球范围内爆发了水痘(以前称为猴痘),受影响不成比例的同性恋,双性恋,和其他和男人发生性关系的男人.超过35%和40%的水痘病例患有艾滋病毒合并感染和性传播感染(STIs)(例如,沙眼衣原体,淋病奈瑟菌,梅毒螺旋体,和单纯疱疹病毒),分别。也可能发生细菌重叠感染。MPXV和其他感染因子的共同感染可能会增加疾病的严重程度,恶化的结果,延长恢复过程,并可能导致随后疾病的发病率和死亡率。然而,MPXV和HIV之间的相互作用,细菌,其他STI病原体和宿主细胞研究甚少。关于艾滋病毒共同感染的影响,有许多悬而未决的问题,性传播感染,或细菌超感染对MPXV感染的诊断和治疗,包括临床和实验室确诊的痘诊断,治疗效果欠佳,并诱导抗病毒药物的耐药性。在这篇评论文章中,我们将讨论MPXV生物学的进展和知识差距,抗病毒治疗,人类MPXV的发病机制及其与HIV的共同感染,性传播感染,或细菌超感染,以及共感染对水痘诊断和治疗的影响。这篇综述不仅阐明了MPXV感染和其他病原体的共同感染,而且呼吁对MPXV生命周期以及MPXV和其他感染因子共同感染的发病机理的分子机制进行更多的研究。以及用于检测MPXV和其他STI共感染的新型多重分子检测小组的研究和开发。
    Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022-2023, due to Clade IIb mpox virus (MPXV), disproportionately affected gay, bisexual, and other men who have sex with men. More than 35% and 40% of the mpox cases suffer from co-infection with HIV and sexually transmitted infections (STIs) (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and herpes simplex virus), respectively. Bacterial superinfection can also occur. Co-infection of MPXV and other infectious agents may enhance disease severity, deteriorate outcomes, elongate the recovery process, and potentially contribute to the morbidity and mortality of the ensuing diseases. However, the interplays between MPXV and HIV, bacteria, other STI pathogens and host cells are poorly studied. There are many open questions regarding the impact of co-infections with HIV, STIs, or bacterial superinfections on the diagnosis and treatment of MPXV infections, including clinical and laboratory-confirmed mpox diagnosis, suboptimal treatment effectiveness, and induction of antiviral drug resistance. In this review article, we will discuss the progress and knowledge gaps in MPXV biology, antiviral therapy, pathogenesis of human MPXV and its co-infection with HIV, STIs, or bacterial superinfections, and the impact of the co-infections on the diagnosis and treatment of mpox disease. This review not only sheds light on the MPXV infection and co-infection of other etiologies but also calls for more research on MPXV life cycles and the molecular mechanisms of pathogenesis of co-infection of MPXV and other infectious agents, as well as research and development of a novel multiplex molecular testing panel for the detection of MPXV and other STI co-infections.
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  • 文章类型: Journal Article
    2022年,一些国家爆发了前所未有的水痘疫情。与正痘病毒的估计比率相比,2022年爆发的序列显示出更高的核苷酸取代。最近,已经描述了病变内SNV(单核苷酸变体),这些被认为是遗传变异的可能来源。直到现在,尚不清楚几种SNV的存在是否代表局部诱变或可能的共感染的结果。我们通过对四个无关的水痘病例进行全基因组测序分析,调查了SNV的重要性。除了流行病毒株(MPXV)所携带的已知突变外,确定了7个新的突变,包括位于参与免疫逃避机制和/或病毒适应性的基因中的SNV,其中六个似乎是APOBEC3驱动的。有趣的是,3例患者表现出5种非同义变异的突变和野生型等位基因共存.此外,两个病人,显然无关,显示了两个新突变的类似模式,尽管频率不同。混合病毒种群的共存,患者体内有非同义突变,支持可能合并感染的假设。更大的临床队列的额外调查对于验证患者内病毒基因组异质性和确定稍微不同的MPXV毒株共存事件的可能性是必不可少的。
    In 2022, an unprecedented outbreak of mpox raged in several nations. Sequences from the 2022 outbreak reveal a higher nucleotide substitution if compared with the estimated rate for orthopoxviruses. Recently, intra-lesion SNVs (single nucleotide variants) have been described, and these have been suggested as possible sources of genetic variation. Until now, it has not been clear if the presence of several SNVs could represents the result of local mutagenesis or a possible co-infection. We investigated the significance of SNVs through whole-genome sequencing analysis of four unrelated mpox cases. In addition to the known mutations harboured by the circulating strains of virus (MPXV), 7 novel mutations were identified, including SNVs located in genes that are involved in immune evasion mechanisms and/or viral fitness, six of these appeared to be APOBEC3-driven. Interestingly, three patients exhibited the coexistence of mutated and wild-type alleles for five non-synonymous variants. In addition, two patients, apparently unrelated, showed an analogous pattern for two novel mutations, albeit with divergent frequencies. The coexistence of mixed viral populations, harbouring non-synonymous mutations in patients, supports the hypothesis of possible co-infection. Additional investigations of larger clinical cohorts are essential to validating intra-patient viral genome heterogeneity and determining the possibility of co-presence events of slightly divergent MPXV strains.
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