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基于氨基酸替换的简单机制不是导致日本脑炎病毒感染小鼠高死亡率的关键决定因素。

A Simple Mechanism Based on Amino Acid Substitutions is not a Critical Determinant of High Mortality of Japanese Encephalitis Virus Infection in Mice.

机构信息

Department of Virology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

Leading Graduate School Program, Nagasaki University, Nagasaki 852-8523, Japan.

出版信息

Viruses. 2018 Feb 3;10(2):62. doi: 10.3390/v10020062.

DOI:10.3390/v10020062
PMID:29401664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5850369/
Abstract

For the development of effective treatment strategies for Japanese encephalitis (JE), it is important to identify the viral factors causing severe disease during JE virus (JEV) infection. In this study, we assessed whether amino acid substitutions are critical factors for higher mortality of JaTH160 compared with JaOArS982 in mice using the technique of infectious cDNA clones. We raised the possibility that two amino acids of C and NS3 of JaTH160 may contribute to increased mortality in mice. However, simultaneous substitutions of these amino acids did not significantly increase the virulence of JaOArS982, suggesting that high mortality due to JaTH160 viral infection cannot be simply attributed to the specific amino acids. Multiple and complex, but not simple, mechanisms may induce the high mortality of JaTH160 infection in mice.

摘要

为了开发针对日本脑炎(JE)的有效治疗策略,确定 JEV 感染期间导致严重疾病的病毒因素非常重要。在这项研究中,我们使用传染性 cDNA 克隆技术评估了氨基酸取代是否是 JaTH160 导致比 JaOArS982 更高死亡率的关键因素。我们提出了 JaTH160 的 C 位和 NS3 位的两个氨基酸可能导致小鼠死亡率增加的可能性。然而,这些氨基酸的同时取代并没有显著增加 JaOArS982 的毒力,这表明 JaTH160 病毒感染导致的高死亡率不能简单归因于特定的氨基酸。可能存在多种复杂而非简单的机制导致 JaTH160 感染在小鼠中导致高死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/40d34ee825c2/viruses-10-00062-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/d68c298c0209/viruses-10-00062-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/62d46d6669af/viruses-10-00062-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/a74cda98ab52/viruses-10-00062-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/40d34ee825c2/viruses-10-00062-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/d68c298c0209/viruses-10-00062-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/62d46d6669af/viruses-10-00062-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/a74cda98ab52/viruses-10-00062-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb3/5850369/40d34ee825c2/viruses-10-00062-g004a.jpg

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本文引用的文献

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NS1' Protein Expression in the JaOArS982 Strain of Japanese Encephalitis Virus Does Not Enhance Virulence in Mice.日本脑炎病毒JaOArS982株中NS1'蛋白的表达不会增强小鼠的毒力。
Trop Med Health. 2015 Dec;43(4):233-7. doi: 10.2149/tmh.2015-27. Epub 2015 Aug 20.
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A Single Amino Acid Substitution in the NS2A Protein of Japanese Encephalitis Virus Affects Virus Propagation In Vitro but Not In Vivo.日本脑炎病毒NS2A蛋白中的单个氨基酸取代影响病毒体外增殖但不影响体内增殖。
J Virol. 2015 Jun;89(11):6126-30. doi: 10.1128/JVI.00370-15. Epub 2015 Mar 18.
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Virol J. 2014 Jun 5;11:105. doi: 10.1186/1743-422X-11-105.
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A critical determinant of neurological disease associated with highly pathogenic tick-borne flavivirus in mice.与高致病性蜱传黄病毒相关的神经疾病的关键决定因素。
J Virol. 2014 May;88(10):5406-20. doi: 10.1128/JVI.00421-14. Epub 2014 Feb 26.
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NS1' protein expression facilitates production of Japanese encephalitis virus in avian cells and embryonated chicken eggs.NS1' 蛋白表达促进了日本脑炎病毒在禽类细胞和鸡胚中的生产。
J Gen Virol. 2014 Feb;95(Pt 2):373-383. doi: 10.1099/vir.0.057968-0.
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A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1' formation and contributes to attenuation.日本脑炎活疫苗病毒(SA14-14-2)NS2A 中的单个核苷酸突变可消除 NS1'的形成并有助于减毒。
J Gen Virol. 2012 Sep;93(Pt 9):1959-1964. doi: 10.1099/vir.0.043844-0. Epub 2012 Jun 27.
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Overview: Japanese encephalitis.概述:日本脑炎。
Prog Neurobiol. 2010 Jun;91(2):108-20. doi: 10.1016/j.pneurobio.2010.01.008. Epub 2010 Feb 2.
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A single mutation in the Japanese encephalitis virus E protein (S123R) increases its growth rate in mouse neuroblastoma cells and its pathogenicity in mice.日本脑炎病毒 E 蛋白(S123R)中的单个突变提高了其在小鼠神经母细胞瘤细胞中的生长速度和在小鼠中的致病性。
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