Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis.
Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis.
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DOI：
10.1016/j.jmb.2016.05.008
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发表时间：
2016-08-28
影响因子：
5.6
通讯作者：
Ebihara, Hideki
中科院分区：
文献类型：
--
作者：
Banadyga, Logan;Dolan, Michael A.;Ebihara, Hideki
埃博拉病毒、马尔堡病毒和拉文病毒都是丝状病毒，是严重出血热的病原体。我们对丝状病毒病发病机制的了解大部分来自动物模型的研究，包括非人灵长类动物（NHP），这些动物被认为是“金标准”丝状病毒模型，因为它们忠实地概括了丝状病毒病的临床特征。然而，啮齿动物模型，包括小鼠、豚鼠和仓鼠，也存在埃博拉病毒、马尔堡病毒和Ravn病毒的模型，尽管它们可能无法重现丝状病毒病的所有临床体征，但由于其相对易于使用和成本低，它们通常是病毒发病机制初步描述和抗病毒药物和治疗评价的首选。由于丝状病毒在成年免疫活性啮齿动物中不会引起显著疾病，因此这些模型依赖于“啮齿动物适应性”病毒，这些病毒已通过其宿主传代多次，直至达到毒力和致死性。在适应过程中，病毒获得了许多核苷酸/氨基酸突变，这些突变有助于在啮齿动物宿主中产生毒力。有趣的是，病毒蛋白24（VP 24）和核蛋白（NP）似乎是埃博拉病毒在啮齿动物中的主要毒力因子，而VP 40似乎是马尔堡病毒的主要毒力因子。通过表征这些突变并了解导致获得毒力的分子机制，我们可以更好地了解人类丝状病毒病的致病过程。这些过程以及对它们有贡献的病毒和/或细胞蛋白质将成为开发新型治疗方法和对策的有吸引力的目标。
Ebola, Marburg, and Ravn virus, all filoviruses, are the causative agents of severe hemorrhagic fever. Much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including non-human primates (NHPs), which are considered the “gold standard” filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. However, rodent models, including the mouse, guinea pig, and hamster, also exist for Ebola, Marburg, and Ravn viruses, and although they may not reproduce all the clinical signs of filovirus disease, thanks to their relative ease-of-use and low cost they are often the first choice for initial descriptions of virus pathogenesis and evaluation of anti-viral prophylactics and therapeutics. Since filoviruses do not cause significant disease in adult, immunocompetent rodents, these models rely on “rodent-adapted” viruses that have been passaged several times through their host until virulence and lethality are achieved. In the process of adaptation, the viruses acquire numerous nucleotide/amino acid mutations that contribute to virulence in their rodent host. Interestingly, virus protein 24 (VP24) and nucleoprotein (NP) appear to be major virulence factors for ebolaviruses in rodents, whereas VP40 appears to be the major virulence factor for marburgviruses. By characterizing these mutations and understanding the molecular mechanisms that lead to the acquisition of virulence, we can gain better insight into the pathogenic processes that underlie filovirus disease in humans. These processes, and the viral and/or cellular proteins that contribute to them, will make attractive targets for the development of novel therapeutics and countermeasures.
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影响因子：
3.7
作者：
Beniac DR;Melito PL;Devarennes SL;Hiebert SL;Rabb MJ;Lamboo LL;Jones SM;Booth TF
通讯作者：
Booth TF
影响因子：
2.7
作者：
BUKREYEV, AA;VOLCHKOV, VE;NETESOV, SV
通讯作者：
NETESOV, SV
影响因子：
6.4
作者：
Brannan, Jennifer M.;Froude, Jeffery W.;Dye, John M.
通讯作者：
Dye, John M.
影响因子：
5.4
作者：
Adam, B;Lins, L;Brasseur, R
通讯作者：
Brasseur, R
影响因子：
3.7
作者：
Becker, S;Rinne, C;Mühlberger, E
通讯作者：
Mühlberger, E