Arenavirus Quasispecies and Their Biological Implications.
Arenavirus Quasispecies and Their Biological Implications.
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DOI：
10.1007/82_2015_468
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发表时间：
2016
影响因子：
--
通讯作者：
de la Torre JC
中科院分区：
文献类型：
--
作者：
Grande-Pérez A;Martin V;Moreno H;de la Torre JC
沙粒病毒科目前包括20多种病毒，每一种病毒都与一种主要的啮齿动物有关，作为自然宿主，在一种情况下可能与层状蝙蝠有关。此外，最近的发现已经在圈养的蛇中记录了一组不同的沙粒病毒。人类感染是通过粘膜暴露于气溶胶或通过磨损的皮肤与传染性物质直接接触而发生的。沙状病毒值得关注，因为它既可以作为研究急性和持续性感染的高度可控的实验模型系统，也可以作为临床重要的人类病原体，包括拉沙（LASV）和朱宁（JUNV）病毒，分别是拉沙和阿根廷出血热（ahf）的病原体，目前还没有fda许可的疫苗，目前的治疗仅限于在标签外使用利巴韦林（Rib），这有很大的局限性。沙粒病毒是具有双片段负链RNA基因组的包膜病毒。每个基因组片段L（约7.3 kb）和S（约3.5 kb）使用双义编码策略来指导两个方向相反的多肽的合成，由非编码基因间区（IGR）分隔。S基因组RNA编码病毒核蛋白（NP）和病毒表面糖蛋白前体（GPC），介导病毒受体识别和通过内吞作用进入细胞。L基因组RNA编码病毒RNA依赖的RNA聚合酶（RdRp，或L聚合酶）和小的（约11kda）无名指蛋白Z，后者具有真正基质蛋白的功能，包括指导病毒出芽。沙粒病毒被认为具有相对稳定的遗传特性，其种内和种间氨基酸序列的同源性分别为90 - 95%和44 - 63%。然而，最近的证据表明，该领域存在广泛的沙粒病毒遗传变异。此外，在密切相关的LCMV分离株之间已经记录了显著的表型差异。这些数据为病毒准种参与沙粒病毒的适应性和发病机制提供了强有力的证据。在这里，我们将回顾几个方面的沙粒病毒的分子生物学，系统发育和进化，以及准种动态的沙粒病毒种群更好地了解沙粒病毒的发病机制，以及开发新的抗病毒策略，以对抗沙粒病毒感染。
The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly phyllostomid bats. Moreover, recent findings have documented a divergent group of arenaviruses in captive alethinophidian snakes. Human infections occur through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials. Arenaviruses merit interest both as highly tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens including Lassa (LASV) and Junin (JUNV) viruses, the causative agents of Lassa and Argentine hemorrhagic fevers (AHFs), respectively, for which there are no FDA-licensed vaccines, and current therapy is limited to an off-label use of ribavirin (Rib) that has significant limitations. Arenaviruses are enveloped viruses with a bi-segmented negative strand (NS) RNA genome. Each genome segment, L (ca 7.3 kb) and S (ca 3.5 kb), uses an ambisense coding strategy to direct the synthesis of two polypeptides in opposite orientation, separated by a noncoding intergenic region (IGR). The S genomic RNA encodes the virus nucleoprotein (NP) and the precursor (GPC) of the virus surface glycoprotein that mediates virus receptor recognition and cell entry via endocytosis. The L genome RNA encodes the viral RNA-dependent RNA polymerase (RdRp, or L polymerase) and the small (ca 11 kDa) RING finger protein Z that has functions of a bona fide matrix protein including directing virus budding. Arenaviruses were thought to be relatively stable genetically with intra- and interspecies amino acid sequence identities of 90–95 % and 44–63 %, respectively. However, recent evidence has documented extensive arenavirus genetic variability in the field. Moreover, dramatic phenotypic differences have been documented among closely related LCMV isolates. These data provide strong evidence of viral quasispecies involvement in arenavirus adaptability and pathogenesis. Here, we will review several aspects of the molecular biology of arenaviruses, phylogeny and evolution, and quasispecies dynamics of arenavirus populations for a better understanding of arenavirus pathogenesis, as well as for the development of novel antiviral strategies to combat arenavirus infections.
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