The SI strain of measles virus derived from a patient with subacute sclerosing panencephalitis possesses typical genome alterations and unique amino acid changes that modulate receptor specificity and reduce membrane fusion activity
The SI strain of measles virus derived from a patient with subacute sclerosing panencephalitis possesses typical genome alterations and unique amino acid changes that modulate receptor specificity and reduce membrane fusion activity
复制标题
源自亚急性硬化性全脑炎患者的麻疹病毒 SI 株具有典型的基因组改变和独特的氨基酸变化，可调节受体特异性并降低膜融合活性
DOI：
10.1128/jvi.05067-11
复制
发表时间：
2011
影响因子：
5.4
通讯作者：
Takeda M
中科院分区：
文献类型：
--
作者：
Seki F;Yamada K;Nakatsu Y;Okamura K;Yanagi Y;Nakayama T;Komase K;Takeda M
亚急性硬化性全脑炎（SSPE）是一种与麻疹相关的致命后遗症，由麻疹病毒（MV）持续感染大脑引起。SI菌株于1976年从一名SSPE患者中分离出来，在动物中显示神经毒力。基因组核苷酸序列分析表明，SI株基因组具有典型的SSPE衍生菌株的基因组改变，即M蛋白中积累的氨基酸取代和F蛋白的胞质尾截短。通过建立高效的反向遗传学系统，获得了表达绿色荧光蛋白的重组SI菌株（rSI-AcGFP）。通过荧光显微镜评价rSI-AcGFP对各种细胞类型的感染。rSI-AcGFP表现出有限的合胞体形成活性，并且在细胞中扩散较差。使用具有SI株和野生型MV株之间的嵌合基因组的重组MV的分析表明，膜相关蛋白基因（M，F和H）是负责SI株的生长表型改变。病毒糖蛋白的功能分析表明，SI株的F蛋白由于E300 G取代而表现出降低的融合活性，并且SI株的H蛋白由于L482 F、S546 G和F555 L取代而有效地利用了CD 46，但利用免疫和上皮细胞上的原始MV受体的能力较差。在本研究中获得的数据提供了一个新的平台，用于分析SSPE衍生的菌株，以及一个明确的例子，SSPE衍生的菌株，表现出改变的受体特异性和有限的融合活性。
Subacute sclerosing panencephalitis (SSPE) is a fatal sequela associated with measles and is caused by persistent infection of the brain with measles virus (MV). The SI strain was isolated in 1976 from a patient with SSPE and shows neurovirulence in animals. Genome nucleotide sequence analyses showed that the SI strain genome possesses typical genome alterations for SSPE-derived strains, namely, accumulated amino acid substitutions in the M protein and cytoplasmic tail truncation of the F protein. Through the establishment of an efficient reverse genetics system, a recombinant SI strain expressing a green fluorescent protein (rSI-AcGFP) was generated. The infection of various cell types with rSI-AcGFP was evaluated by fluorescence microscopy. rSI-AcGFP exhibited limited syncytium-forming activity and spread poorly in cells. Analyses using a recombinant MV possessing a chimeric genome between those of the SI strain and a wild-type MV strain indicated that the membrane-associated protein genes (M, F, and H) were responsible for the altered growth phenotype of the SI strain. Functional analyses of viral glycoproteins showed that the F protein of the SI strain exhibited reduced fusion activity because of an E300G substitution and that the H protein of the SI strain used CD46 efficiently but used the original MV receptors on immune and epithelial cells poorly because of L482F, S546G, and F555L substitutions. The data obtained in the present study provide a new platform for analyses of SSPE-derived strains as well as a clear example of an SSPE-derived strain that exhibits altered receptor specificity and limited fusion activity.