Haller Otto, Staeheli Peter, Kochs Georg
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
Biochimie. 2007 Jun-Jul;89(6-7):812-8. doi: 10.1016/j.biochi.2007.04.015. Epub 2007 May 8.
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-I-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.
Mx蛋白是许多物种中由干扰素诱导产生的抗病毒状态的关键组成部分。它们属于发动蛋白样大GTP酶（GTPases）家族，已知该家族参与细胞内囊泡运输和细胞器稳态。Mx GTP酶与发动蛋白具有结构和功能特性，如自我组装以及与细胞内膜的结合。一些Mx GTP酶的独特特性是它们对多种RNA病毒具有抗病毒活性，包括流感病毒和布尼亚病毒科成员。这些病毒在其生命周期的早期阶段受到抑制，即在宿主细胞进入后不久且在基因组扩增之前。小鼠Mx1 GTP酶在细胞核中积累，在那里它与早幼粒细胞白血病（PML）核体的成分结合，并抑制已知在细胞核中复制的流感病毒和托高托病毒。人MxA GTP酶在细胞质中积累，并部分与内质网的COP-I阳性亚区室相关。这个膜区室似乎提供了一个促进病毒靶标识别的相互作用平台。对于布尼亚病毒，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。对于托高托病毒，MxA识别病毒核蛋白并阻止进入的病毒核衣壳被转运到病毒转录和复制的细胞核中。在这两种情况下，MxA的GTP结合和羧基末端效应器功能对于靶标识别都是必需的。一般来说，Mx GTP酶似乎通过感知核衣壳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。
