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Basic Characteristics of Mutations
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Mutation Site
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K279M |
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Mutation Site Sentence
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In addition mutations E138K, E244G, and K279M were observed in the SA14-14-2 (Supplementary Table 2) and were also reported to be involved in neurovirulence in mice. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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E |
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Standardized Encoding Gene
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envelope
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Genotype/Subtype
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- |
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Viral Reference
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D90195;D90194;AY849939
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
|
- |
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Location
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- |
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Literature Information
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PMID
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28446752
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Title
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Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability
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Author
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Wang X,Li SH,Zhu L,Nian QG,Yuan S,Gao Q,Hu Z,Ye Q,Li XF,Xie DY,Shaw N,Wang J,Walter TS,Huiskonen JT,Fry EE,Qin CF,Stuart DI,Rao Z
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Journal
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Nature communications
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Journal Info
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2017 Apr 26;8(1):14
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Abstract
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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.Japanese encephalitis virus (JEV) is a Flavivirus responsible for thousands of deaths every year for which there are no specific anti-virals. Here, Wang et al. report the cryo-EM structure of mature JEV at near-atomic resolution and identify structural elements that modulate stability and virulence.
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Sequence Data
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-
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