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现在位置:首页 > 科研进展 > 最新重要论文(影响因子PNAS及以上)
Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability, Nature Communications 8, Article number: 14 (2017)
2017-04-27 | 【     】【打印】【关闭

Nature Communications 8, Article number: 14 (2017) doi:10.1038/s41467-017-00024-6,Received:06 July 2016,Accepted:16 February 2017,Published online:26 April 2017

Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability

Xiangxi Wang, Shi-Hua Li, Ling Zhu, Qing-Gong Nian, Shuai Yuan, Qiang Gao, Zhongyu Hu, Qing Ye, Xiao-Feng Li, Dong-Yang Xie, Neil Shaw, Junzhi Wang, Thomas S. Walter, Juha T. Huiskonen, Elizabeth E. Fry, Cheng-Feng Qin, David I. Stuart & Zihe Rao

Abstract

Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual “hole” on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice. We also identify structural elements modulating viral stability, notably Gln264 of E, which, when replaced by His264 strengthens a hydrogen-bonding network, leading to a more stable virus. These studies unveil determinants of neurovirulence and stability in Japanese encephalitis virus, opening up new avenues for therapeutic interventions against neurotropic flaviviruses.

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201704/t20170427_4781070.html

文章链接:http://www.nature.com/articles/s41467-017-00024-6

 

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