A single adaptive point mutation in Japanese encephalitis virus capsid is sufficient to render the virus as a stable vector for gene delivery

A single adaptive point mutation in Japanese encephalitis virus capsid is sufficient to render the virus as a stable vector for gene delivery
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日本脑炎病毒衣壳中的单个适应性点突变足以使该病毒成为基因传递的稳定载体

DOI:
10.1016/j.virol.2016.01.001
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发表时间:
2016-03-01
期刊:
影响因子:
3.7
通讯作者:
Xu, Fuqiang
Xu, Fuqiang
中科院分区:
医学3区
文献类型:
--
作者:
Jia, Fan;Zhu, Xutao;Xu, Fuqiang

文献摘要

被引文献

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日本脑炎病毒(Japanese encephalitis virus,JEV)是一种嗜神经性黄病毒,具有广泛的宿主。目前尚无稳定的JEV载体的报道。在此,我们通过将08(衣壳的N-末端38个氨基酸)-EGFP-FMDV 2A的片段插入到衣壳基因的5 'UTR和N-末端之间的连接处来构建JEV-EGFP。通过基因组测序鉴定了一个适应性核苷酸突变T45 G(位于衣壳基因的N-末端),导致氨基酸从天冬酰胺变为赖氨酸(N15 K)。它稳定了载体并扩大了病毒粒子。稳定效果可能是普遍的,因为当EGFP被另一种标记SNAP取代时,它也是稳定的。根据以前发表的和我们的数据,提出了一个模型,这种稳定效果。这一发现可用于构建各种基于JEV的稳定递送系统,用于病毒学研究和神经回路追踪。(C)2016 Elsevier Inc. All rights reserved.
Japanese encephalitis virus (JEV) is a neurotropic flavivirus that has broad range of hosts. Stable JEV vector has not been reported yet. Here, we constructed a JEV-EGFP by inserting a fragment of 08 (the N-terminal 38 amino acids of capsid)-EGFP-FMDV2A into the junction between 5'UTR and the N-terminus of capsid gene. An adaptive nucleotide mutation T45G (location at the N-terminus of capsid gene), resulting in an amino acid change from asparagine to lysine (N15K), was identified by genome sequencing. It stabilized the vector and enlarged the virion. The stabilizing effect might be general because it is also stable when EGFP was replaced with another marker, SNAP. A model was proposed for this stabilization effect based on previously published and our data. This finding may be used to construct various JEV-based stable delivery systems for virological studies and neural circuit tracing. (C) 2016 Elsevier Inc. All rights reserved.