Dengue virus M protein contains a proapoptotic sequence referred to as ApoptoM
Dengue virus M protein contains a proapoptotic sequence referred to as ApoptoM
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DOI：
10.1099/vir.0.19163-0
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发表时间：
2003-10-01
影响因子：
3.8
通讯作者：
Desprès, P
中科院分区：
文献类型：
--
作者：
Catteau, A;Kalinina, O;Desprès, P
登革（DEN）病毒诱导细胞凋亡是一种显著的细胞病变效应。需要解决的关键问题之一是哪些病毒成分诱导DEN病毒感染细胞的凋亡。本研究探讨了小膜蛋白（M）是否参与了DEN病毒诱导细胞凋亡的过程。通过使用一系列增强的绿色荧光蛋白融合DEN蛋白来解决这一问题。提供的证据表明，所有四种DEN血清型的M胞外域（残基M-1至M-40）的细胞内产生触发宿主细胞如小鼠神经母细胞瘤的凋亡。Neuro 2a和人肝癌HepG 2细胞。日本脑炎病毒、西尼罗河病毒和黄热病病毒的野生型毒株的M胞外域也具有促凋亡特性。M胞外域从高尔基体到质膜的出口似乎是启动细胞凋亡所必需的。该研究发现，抗凋亡蛋白Bcl-2保护HepG 2细胞免受DEN M胞外域的促死亡活性。这表明M胞外域通过激活线粒体凋亡途径发挥其细胞毒性作用。DEN M胞外域的细胞毒性反映了命名为ApoptoM的9个羧基末端氨基酸（残基M-32至M-40）的内在促凋亡特性。残基M-36是独特的，因为它调节M胞外域的促死活性。确定导致细胞凋亡的ApoptoM激活信号通路将为研究M蛋白如何在黄病毒感染细胞的命运中发挥关键作用提供基础。
The induction of apoptotic cell death is a prominent cytopathic effect of dengue (DEN) viruses. One of the key questions to be addressed is which viral components induce apoptosis in DEN virus-infected cells. This study investigated whether the small membrane (M) protein was involved in the induction of apoptosis by DEN virus. This was addressed by using a series of enhanced green fluorescent protein-fused DEN proteins. Evidence is provided that intracellular production of the M ectodomains (residues M-1 to M-40) of all four DEN serotypes triggered apoptosis in host cells such as mouse neuroblastoma. Neuro 2a and human hepatoma HepG2 cells. The M ectodomains of the wild-type strains of Japanese encephalitis, West Nile and yellow fever viruses also had proapoptotic properties. The export of the M ectodomain from the Golgi apparatus to the plasma membrane appeared to be essential for the initiation of apoptosis. The study found that anti-apoptosis protein Bcl-2 protected HepG2 cells against the death-promoting activity of the DEN M ectodomain. This suggests that the M ectodomain exerts its cytotoxic effects by activating a mitochondrial apoptotic pathway. The cytotoxicity of the DEN M ectodomain reflected the intrinsic proapoptotic properties of the nine carboxy-terminal amino acids (residues M-32 to M-40) designated ApoptoM. Residue M-36 was unique in that it modulated the death-promoting activity of the M ectodomain. Defining the ApoptoM-activated signalling pathways leading to apoptosis will provide the basis for studying how the M protein might play a key role in the fate of the flavivirus-infected cells.