Interferon-induced Mx proteins in antiviral host defense
Interferon-induced Mx proteins in antiviral host defense
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DOI：
10.1016/j.biochi.2007.04.015
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发表时间：
2007-06-01
期刊：
影响因子：
3.9
通讯作者：
Kochs, Georg
中科院分区：
文献类型：
--
作者：
Haller, Otto;Staeheli, Peter;Kochs, Georg
在许多物种中，Mx蛋白是干扰素诱导的抗病毒状态的关键组分。它们属于动力蛋白样大的鸟苷三磷酸酶（GTP酶）类，已知参与胞内囊泡运输和细胞器稳态。Mx GTP酶与发动蛋白具有相同的结构和功能特性，例如自组装和与细胞内膜的结合。一些Mx GTP酶的独特性质是它们对广泛的RNA病毒（包括流感病毒和布尼亚病毒家族的成员）的抗病毒活性。这些病毒在其生命周期的早期阶段，即进入宿主细胞后不久和基因组扩增前被抑制。小鼠Mx 1 GT3在细胞核中蓄积，在那里与PML核体的组分结合，并抑制已知在细胞核中复制的流感病毒和Thogoto病毒。人MxA GT3在细胞质中积累，并部分与内质网的COP-1阳性亚室相关。这种膜隔室似乎提供了一个相互作用的平台，有利于病毒的目标识别。在布尼亚病毒的情况下，MxA识别病毒核衣壳蛋白并干扰其在病毒基因组复制中的作用。在Thogoto病毒的情况下，MxA识别病毒核蛋白并阻止进入的病毒核衣壳被转运到细胞核中，细胞核是病毒转录和复制的位点。在这两种情况下，MxA的GTP结合和羧基末端效应子功能是靶点识别所必需的。一般而言，Mx GTP酶似乎通过感测核帽样结构来检测病毒感染。因此，这些病毒成分被捕获并分选到它们无法用于产生新病毒颗粒的位置。(C)2007年，Elsevier Masson SAS。All rights reserved.
Mx proteins are key components of the antiviral state induced by interferons in many species. They belong to the class of dynamin-like large guanosine triphosphatases (GTPases) known to be involved in intracellular vesicle trafficking and organelle homeostasis. Mx GTPases share structural and functional properties with dynamin, such as self-assembly and association with intracellular membranes. A unique property of some Mx GTPases is their antiviral activity against a wide range of RNA viruses, including influenza viruses and members of the bunyavirus family. These viruses are inhibited at an early stage in their life cycle, soon after host cell entry and before genome amplification. The mouse Mx1 GTPase accumulates in the cell nucleus where it associates with components of the PML nuclear bodies and inhibits influenza and Thogoto viruses known to replicate in the nucleus. The human MxA GTPase accumulates in the cytoplasm and is partly associated with a COP-1-positive subcompartment of the endoplasmic reticulum. This membrane compartment seems to provide an interaction platform that facilitates viral target recognition. In the case of bunyaviruses, MxA recognizes the viral nucleocapsid protein and interferes with its role in viral genome replication. In the case of Thogoto virus, MxA recognizes the viral nucleoprotein and prevents the incoming viral nucleocapsids from being transported into the nucleus, the site of viral transcription and replication. In both cases, GTP-binding and carboxy-terminal effector functions of MxA are required for target recognition. In general, Mx GTPases appear to detect viral infection by sensing nucleocapsid-like structures. As a consequence, these viral components are trapped and sorted to locations where they become unavailable for the generation of new virus particles. (C) 2007 Elsevier Masson SAS. All rights reserved.