Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis
Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis
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DOI：
10.1016/j.virol.2015.10.004
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发表时间：
2016-01-01
期刊：
影响因子：
3.7
通讯作者：
Ogura, Hisashi
中科院分区：
文献类型：
--
作者：
Ayata, Minoru;Tanaka, Miyuu;Ogura, Hisashi
麻疹病毒（MV）是亚急性硬化性全脑炎（SSPE）的病原体。我们以前报道，F基因的SSPE大坂-2株是MV神经毒力的主要决定因素。由于SSPE毒株之间突变的位点和程度不同，因此有必要确定导致单个病毒株的SSPE特异性表型的突变。在本研究中，在IC 323野生型MV背景下生成了含有来自SSPE Osaka-1株的病毒相关基因的重组病毒。仓鼠接种MV含有大坂-1株的H基因表现出多动症和癫痫发作，但通常恢复和存活。接种含有大坂-1株F基因的MV的仓鼠表现出严重的神经系统症状并死亡。F蛋白的七肽重复A和C区的氨基酸取代，包括氨基酸94处的甲硫氨酸至缬氨酸取代，在神经毒力中起主要作用。(C)2015 Elsevier Inc. All rights reserved.
Measles virus (MV) is the causative agent of subacute sclerosing panencephalitis (SSPE). We previously reported that the F gene of the SSPE Osaka-2 strain is the major determinant of MV neurovirulence. Because the sites and extents of mutations differ among SSPE strains, it is necessary to determine the mutations responsible for the SSPE-specific phenotypes of individual viral strain. In this study, recombinant viruses containing the envelope-associated genes from the SSPE Osaka-1 strain were generated in the IC323 wild-type MV background. Hamsters inoculated with MV containing the H gene of the Osaka-1 strain displayed hyperactivity and seizures, but usually recovered and survived. Hamsters inoculated with MV containing the F gene of the Osaka-1 strain displayed severe neurologic signs and died. Amino acid substitutions in the heptad repeat A and C regions of the F protein, including a methionine-to-valine substitution at amino acid 94, play major roles in neurovirulence. (C) 2015 Elsevier Inc. All rights reserved.