Functional analysis of picornavirus 2B proteins: Effects on calcium homeostasis and intracellular protein trafficking
Functional analysis of picornavirus 2B proteins: Effects on calcium homeostasis and intracellular protein trafficking
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DOI：
10.1128/jvi.02076-07
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
van Kuppeveld, Frank J. M.
中科院分区：
文献类型：
--
作者：
de Jong, Arjan S.;de Mattia, Fabrizio;van Kuppeveld, Frank J. M.
小核糖核酸病毒科由一大群正链RNA病毒组成，它们具有相似的基因组组织。小核糖核酸病毒蛋白的命名是基于它们在病毒RNA基因组中的位置，但并不一定意味着不同属蛋白质的保守功能。肠病毒2B蛋白是一种小的疏水蛋白，在个体表达时，定位于内质网（ER）和高尔基复合体，降低内质网和高尔基复合体Ca2+水平，最有可能通过形成跨膜孔，并抑制蛋白质通过高尔基复合体的运输。目前对其他小核糖核酸病毒2B蛋白的功能知之甚少。本研究表明鼻病毒2B在系统发育上与肠病毒2B密切相关，并表现出与肠病毒2B相似的亚细胞定位和功能。相比之下，甲型肝炎病毒、口蹄疫病毒和脑心肌炎病毒的2B蛋白与肠道病毒的亲缘关系更远，它们的定位不同，对Ca2+稳态和细胞内蛋白运输的影响很小，如果有的话。我们的数据表明，肠病毒和鼻病毒的2B蛋白在病毒复制中具有相同的功能，而其他小核糖核酸2B蛋白以不同的方式支持病毒的生命周期。此外，我们发现保留在内质网中的肠病毒2B蛋白不能改变Ca2+稳态和抑制蛋白质运输，这表明高尔基复合体定位对其功能的重要性。
The family Picornaviridae consists of a large group of plus-strand RNA viruses that share a similar genome organization. The nomenclature of the picornavirus proteins is based on their position in the viral RNA genome but does not necessarily imply a conserved function of proteins of different genera. The enterovirus 2B protein is a small hydrophobic protein that, upon individual expression, is localized to the endoplasmic reticulum (ER) and the Golgi complex, reduces ER and Golgi complex Ca2+ levels, most likely by forming transmembrane pores, and inhibits protein trafficking through the Golgi complex. At present, little is known about the function of the other picornavirus 2B proteins. Here we show that rhinovirus 2B, which is phylogenetically closely related to enterovirus 2B, shows a similar subcellular localization and function to those of enterovirus 2B. In contrast, 2B proteins of hepatitis A virus, foot-and-mouth disease virus, and encephalomyocarditis virus, all of which are more distantly related to enteroviruses, show a different localization and have little, if any, effects on Ca2+ homeostasis and intracellular protein trafficking. Our data suggest that the 2B proteins of enterovirus and rhinovirus share the same function in virus replication, while the other picornavirus 2B proteins support the viral life cycle in a different manner. Moreover, we show that an enterovirus 2B protein that is retained in the ER is unable to modify Ca2+ homeostasis and inhibit protein trafficking, demonstrating the importance of Golgi complex localization for its functioning.