| Autor: |
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, Walter, Thomas S., Huiskonen, Juha T., Fry, Elizabeth E., Cheng-Feng Qin, Stuart, David I., Rao, Zihe |
| Zdroj: |
Nature Communications; Apr2017, Vol. 8 Issue 4, p1-9, 9p, 5 Color Photographs, 1 Graph |
| Abstrakt: |
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 encephaliticspecific 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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