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Role of RNA-binding proteins during the late stages of Flavivirus replication cycle.
Virology Journal ( IF 4.0 ) Pub Date : 2020-04-25 , DOI: 10.1186/s12985-020-01329-7
Mayra Diosa-Toro 1 , K Reddisiva Prasanth 2 , Shelton S Bradrick 2, 3, 4 , Mariano A Garcia Blanco 1, 2, 4
Affiliation  

The genus Flavivirus encompasses several worldwide-distributed arthropod-borne viruses including, dengue virus, Japanese encephalitis virus, West Nile virus, yellow fever virus, Zika virus, and tick-borne encephalitis virus. Infection with these viruses manifest with symptoms ranging from febrile illness to life- threatening hypotensive shock and encephalitis. Therefore, flaviviruses pose a great risk to public health. Currently, preventive measures are falling short to control epidemics and there are no antivirals against any Flavivirus.Flaviviruses carry a single stranded positive-sense RNA genome that plays multiple roles in infected cells: it is translated into viral proteins, used as template for genome replication, it is the precursor of the subgenomic flaviviral RNA and it is assembled into new virions. Furthermore, viral RNA genomes are also packaged into extracellular vesicles, e.g. exosomes, which represent an alternate mode of virus dissemination.Because RNA molecules are at the center of Flavivirus replication cycle, viral and host RNA-binding proteins (RBPs) are critical determinants of infection. Numerous studies have revealed the function of RBPs during Flavivirus infection, particularly at the level of RNA translation and replication. These proteins, however, are also critical participants at the late stages of the replication cycle. Here we revise the function of host RBPs and the viral proteins capsid, NS2A and NS3, during the packaging of viral RNA and the assembly of new virus particles. Furthermore, we go through the evidence pointing towards the importance of host RBPs in mediating cellular RNA export with the idea that the biogenesis of exosomes harboring Flavivirus RNA would follow an analogous pathway.

中文翻译:

RNA 结合蛋白在黄病毒复制周期后期的作用。

黄病毒属包括几种分布于世界各地的节肢动物传播的病毒,包括登革热病毒、日本脑炎病毒、西尼罗河病毒、黄热病病毒、寨卡病毒和蜱传脑炎病毒。这些病毒感染的症状包括发热性疾病、危及生命的低血压休克和脑炎。因此,黄病毒对公众健康构成巨大风险。目前,预防措施不足以控制流行病,并且没有针对任何黄病毒的抗病毒药物。黄病毒携带单链正义RNA基因组,在受感染的细胞中发挥多种作用:它被翻译成病毒蛋白,用作基因组复制的模板,它是亚基因组黄病毒RNA的前体,并被组装成新的病毒颗粒。此外,病毒RNA基因组也被包装到细胞外囊泡中,例如外泌体,它代表了病毒传播的另一种模式。由于RNA分子位于黄病毒复制周期的中心,因此病毒和宿主RNA结合蛋白(RBP)是病毒传播的关键决定因素。感染。大量研究揭示了 RBP 在黄病毒感染过程中的功能,特别是在 RNA 翻译和复制水平上。然而,这些蛋白质也是复制周期后期的关键参与者。在这里,我们修改了宿主 RBP 和病毒蛋白衣壳、NS2A 和 NS3 在病毒 RNA 包装和新病毒颗粒组装过程中的功能。此外,我们通过证据表明宿主 RBP 在介导细胞 RNA 输出中的重要性,认为含有黄病毒 RNA 的外泌体的生物发生将遵循类似的途径。
更新日期:2020-04-25
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