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[Index par auteur et par numéro de résumé]. [按作者和摘要编号索引]。
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2021-04-01 DOI: 10.1684/vir.2021.0896
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引用次数: 0
Structural and functional characterization of the replication and transcription activities of Hantaan virus polymerase 汉滩病毒聚合酶复制和转录活性的结构和功能表征
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2021-01-01 DOI: 10.1691/ph.2009.0892
S. Garcia, J. Reguera
The Bunyavirales order is a large and worldwide distributed group of segmented negative sense single-stranded RNA viruses (sNSV) that includes more than 350 species (nine families). Arthropods and rodents are their natural reservoirs and humans are occasionally infected resulting in severe diseases. Particularly, the pathogenic prototype viruses Hantaan virus (HTNV, family Hantaviridae) and Crimean-Congo Haemorrhagic fever virus (CCHFV, family Nairoviridae) have increased their geographical expansion and as a consequence, also cases of human diseases. Thus, it is necessary to (i) understand their mechanism of infection and (ii) to develop effective drugs to counteract them. In this perspective, we are working on two critical steps of bunyavirus viral cycle : replication and transcription. These processes are carried out by the multifunctional viral polymerase (L). In order to decipher the molecular mechanisms of bunyavirus replication, we present the study of interactions between hantavirus L proteins and their genomic RNA and replication assays of the full-length Hantaan polymerase. By electrophoresis mobility shifts assays and fluoresce anisotropy we determined the viral sequences specifically binding the L proteins anddefined their length and measured their affinity. We could see differences in the interactions between bunyaviral families L proteins suggesting differences on their mechanisms of replication and the way they are regulated. On the other hand, we performed replication assays for HNTV and LACV L and we have obtained a different result patron. These studies on replication and transcription reactions have shown that Hantaan L is more active than LACV L in the presence or absence of N terminal TAG. Also, the expected replication products are different and we observed some reproducible abortive products.We observed an unexpected UTP transferase activity by the Hantaan L protein that seems related to the processing of its genomic RNA for preventing recognition by the cell innate immune system and maintaining genome integrity. TheseRNA-protein interactions studies, along with the replication assays, will provide the basis for subsequent biochemical and structural studies to understand the molecular mechanism uncovering these reactions. This will be crutial for the development of effective antiviral drugs.
Bunyavirales目是一种分布在世界各地的大型负链单链RNA病毒(sNSV),包括9科350多种。节肢动物和啮齿动物是它们的天然宿主,人类偶尔被感染,导致严重疾病。特别是,致病性原型病毒汉坦病毒(汉坦病毒科)和克里米亚-刚果出血热病毒(克里米亚-刚果出血热病毒科)扩大了其地域范围,因此也增加了人类疾病病例。因此,有必要(1)了解它们的感染机制和(2)开发有效的药物来对抗它们。从这个角度来看,我们正在研究布尼亚病毒周期的两个关键步骤:复制和转录。这些过程是由多功能病毒聚合酶(L)进行的。为了破译布尼亚病毒复制的分子机制,我们研究了汉坦病毒L蛋白与其基因组RNA之间的相互作用,并对全长汉坦聚合酶进行了复制分析。通过电泳迁移率和荧光各向异性测定了特异性结合L蛋白的病毒序列,确定了它们的长度并测量了它们的亲和力。我们可以看到布尼亚病毒家族L蛋白之间相互作用的差异,这表明它们的复制机制和调节方式存在差异。另一方面,我们对HNTV和LACV L进行了复制试验,得到了不同的结果。这些对复制和转录反应的研究表明,无论是否存在N端TAG, Hantaan L都比LACV L更活跃。期望的复制产物也不同,我们观察到一些可复制的流产产物。我们观察到Hantaan L蛋白具有意想不到的UTP转移酶活性,这似乎与其基因组RNA的加工有关,以防止细胞先天免疫系统识别并维持基因组完整性。这些rna -蛋白质相互作用的研究,以及复制试验,将为后续的生化和结构研究提供基础,以了解揭示这些反应的分子机制。这对于开发有效的抗病毒药物至关重要。
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引用次数: 0
[Renaud Mahieux (1968-2020)].
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2020-12-01 DOI: 10.1684/vir.2020.0874
C. Journo, H. Dutartre
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引用次数: 0
Hervé Moreau 16/10/1958 - 05/07/2020.
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2020-08-01 DOI: 10.1684/vir.2020.0855
Gwenaël Piganeau, N. Grimsley
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引用次数: 0
Hervé Moreau 16/10/1958 - 05/07/2020.
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2020-08-01 DOI: 10.1684/vir.2020.0854
G. Piganeau, N. Grimsley
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引用次数: 0
Émergence du coronavirus SARS-CoV-2 : faire face à l’épidémie de Covid-19 冠状病毒SARS-CoV-2的出现:应对Covid-19疫情
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2020-03-01 DOI: 10.1684/VIR.2020.0825
S. V. D. Werf, C. Peltékian
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引用次数: 1
Cell and tissue reservoirs of HIV-1: dynamics during infection. HIV-1的细胞和组织储存库:感染期间的动态。
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2019-07-01 DOI: 10.1684/vir.2019.0784
P. Trémeaux, C. Rouzioux, V. Avettand-Fenoël
Current antiretroviral therapy allows the control of HIV replication but a relapse occurs most of the time in case of treatment interruption. The viral genome integration explains this persistence of HIV in all body tissues, at very variable levels depending on their density of CD4+ T-cells, HIV main target. Secondary lymphoid tissues are the most infected organs. Several techniques can be used to characterize the reservoir, detecting different forms of the virus. They are complementary to decipher the establishment of HIV reservoir during the primary infection and its dynamics afterwards. In peripheral blood, the earlier the initiation of treatment, the more important is the decrease in total HIV DNA. Early treatment prevents the progressive increase in stable integrated forms of HIV DNA and preserves immune cells from infection. A better understanding of HIV infection in controllers will also aid in the development of new therapeutic strategies targeting the reservoir.
目前的抗逆转录病毒治疗可以控制艾滋病毒的复制,但在治疗中断的情况下,大多数情况下会复发。病毒基因组整合解释了艾滋病毒在所有身体组织中持续存在的原因,其水平取决于其CD4+ t细胞的密度,CD4+ t细胞是艾滋病毒的主要目标。继发性淋巴组织是最易感染的器官。有几种技术可用于确定病毒库的特征,检测不同形式的病毒。它们是互补的,可以解释初次感染期间HIV病毒库的建立及其之后的动态。在外周血中,越早开始治疗,总HIV DNA的减少就越重要。早期治疗可防止艾滋病毒DNA稳定整合形式的逐渐增加,并保护免疫细胞免受感染。更好地了解控制者中的HIV感染也将有助于开发针对储存库的新治疗策略。
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引用次数: 1
Viral reservoirs, a challenging theme in HIV research. 病毒库,HIV研究中的一个具有挑战性的主题。
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2019-07-01 DOI: 10.1684/vir.2019.0781
V. Avettand-Fenoël
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引用次数: 0
Viral latency of HIV-1. HIV-1的病毒潜伏期。
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2019-07-01 DOI: 10.1684/vir.2019.0782
S. Bouchat, C. Van Lint
Human immunodeficiency virus (HIV-1) latency is clinically highlighting via the persistence of a residual viral load in cART-treated patients due to the reactivation of cellular reservoirs. Two forms of latency coexist but the contribution of the pre-integrationnal latency clearly plays a minor role in viral persistence. In contrast, the post-integrationnal latency significantly contributes to the evasion of the immune system by the HIV-1 cellular reservoir and consequently to HIV-1 pathogenesis. Although post-transcriptional mechanisms can contribute to the maintenance of viral latency, HIV-1 transcriptional inhibition is critical for the establishment and maintenance of post-integrational latency. This inhibition is a multifactorial phenomenon, making the development of anti-latency therapeutic strategies complex. These different notions will be described throughout this review.
人类免疫缺陷病毒(HIV-1)的潜伏期在临床上是突出的,因为在接受cart治疗的患者中,由于细胞储存库的再激活,残留的病毒载量持续存在。两种形式的潜伏期共存,但整合前潜伏期的贡献显然在病毒持久性中起着次要作用。相反,整合后潜伏期明显有助于HIV-1细胞库逃避免疫系统,从而导致HIV-1发病。尽管转录后机制有助于维持病毒潜伏期,但HIV-1转录抑制对于建立和维持整合后潜伏期至关重要。这种抑制是一个多因素的现象,使得抗潜伏期治疗策略的发展变得复杂。这些不同的概念将在整个审查中描述。
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引用次数: 1
Therapeutic approaches targeting HIV reservoirs. 针对HIV储存库的治疗方法。
IF 0.9 4区 医学 Q4 VIROLOGY Pub Date : 2019-07-01 DOI: 10.1684/vir.2019.0786
A. Chéret
The establishment of latent infection in long-lived cells is the main obstacle to HIV cure or sustained remission without antiretroviral therapy. The most developed therapeutic strategies, in current clinical trials are mainly based on the concept of "shock and kill". They include latency reversing agents (LRAs) to re-activate HIV transcription that can be associated with immunomodulatory treatments. The objective is to eliminate virus-producing cells or to induce the control of HIV after anti-retroviral therapy cessation. HIV reservoir or cancer cells have a number of mechanisms in common. They can escape the immune system and persist by overexpressing survival molecules. This review presents a synthesis of current therapeutic approaches as well as the therapeutic perspectives related to the field of oncology.
在长寿命细胞中潜伏感染的建立是艾滋病毒不经抗逆转录病毒治疗而治愈或持续缓解的主要障碍。在目前的临床试验中,最发达的治疗策略主要是基于“休克和杀伤”的概念。它们包括潜伏期逆转剂(LRAs),可以重新激活与免疫调节治疗相关的HIV转录。目的是消除产生病毒的细胞或在停止抗逆转录病毒治疗后诱导控制艾滋病毒。HIV储存库或癌细胞有许多共同的机制。它们可以逃脱免疫系统,通过过度表达生存分子而存活。本文综述了当前治疗方法的综合以及与肿瘤领域相关的治疗观点。
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引用次数: 0
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Virologie
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