PDF(Pubmed)
Abstract：
Flaviviruses include medically important mosquito-borne pathogens, such as Zika virus (ZIKV), Japanese encephalitis virus (JEV), dengue virus (DENV) and West Nile virus (WNV), that cause hundreds of millions of infections each year. Currently, there are no approved effect therapies against mosquito-borne flaviviruses. The flaviviruses encoded nonstructural protein 1 (NS1) is a secreted glycoprotein widely involved in viral replication, immune evasion, and directly causing tissue-specific damage during flaviviruses infection. Upon viral infection of host cell, NS1 can be found in multiple oligomeric forms and include a dimer on the cell surface, and a soluble secreted hexameric lipoparticle. In the recent decade, the detailed crystal structure of several flaviviruses NS1 have been determined and unraveled its broader and deeper functions. Consistent with the potential immune function revealed by its structure, NS1 is involved in the escaping of host signal immune pathway mediated by pattern recognition receptors (PRRs), including RIG-I-like receptors (RLRS) and Toll-like receptors (TLRs). Moreover, the flavivirus NS1 is efficiently secreted by infected cells and circulates in the blood of the host to directly induce specific tissues damage. The NS1 of ZIKV, JEV and WNV changes the permeability of brain microvascular endothelial cell to cause endothelial cell dysfunction and promote virus pathogenesis. DENV NS1 can induce systemic tissues damage in humans through multiple strategies. Mutations of several key amino acids in NS1 can reduce the neurovirulence of the flavivirus. In this article, we provide an overview of the latest research on this fascinating protein in these disparate areas.
摘要：
黄病毒包括医学上重要的蚊媒病原体，例如寨卡病毒（ZIKV），日本脑炎病毒（JEV），登革热病毒（DENV）和西尼罗河病毒（WNV），每年导致数以亿计的感染。目前,目前尚无针对蚊媒黄病毒的有效疗法。黄病毒编码的非结构蛋白1（NS1）是一种广泛参与病毒复制的分泌型糖蛋白，免疫逃避,并在黄病毒感染期间直接引起组织特异性损伤。在病毒感染宿主细胞时，NS1可以以多种寡聚形式存在，并在细胞表面包括二聚体，和可溶性分泌的六聚体脂质颗粒。在最近的十年里,已经确定了几种黄病毒NS1的详细晶体结构，并揭示了其更广泛和更深的功能。与其结构所揭示的潜在免疫功能一致，NS1参与模式识别受体(PRRs)介导的宿主信号免疫通路的逃逸,包括RIG-I样受体(RLRS)和Toll样受体(TLR)。此外，黄病毒NS1由感染的细胞有效地分泌并在宿主的血液中循环以直接诱导特定组织损伤。ZIKV的NS1,JEV和WNV改变脑微血管内皮细胞的通透性，导致内皮细胞功能障碍，促进病毒发病。DENVNS1可以通过多种策略诱导人体全身组织损伤。NS1中几个关键氨基酸的突变可以降低黄病毒的神经毒力。在这篇文章中,我们提供了在这些不同领域对这种迷人蛋白质的最新研究的概述。
