Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes
Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes
复制标题
DOI：
10.1073/pnas.052430399
复制
发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Haller, O
中科院分区：
文献类型：
--
作者：
Kochs, G;Janzen, C;Haller, O
布尼亚病毒在受感染细胞的细胞质中复制。新的病毒颗粒是通过核衣壳萌芽进入高尔基体而形成的。我们以前已经表明，干扰素诱导的人MxA蛋白抑制布尼亚病毒复制的未知机制。在这里，我们表明，MxA结合到核衣壳蛋白的拉克罗斯病毒（LACV）和共定位与病毒蛋白质的细胞质复合物。电子显微镜观察发现，这些复合物聚集在核周区，由高度有序的晶体结构组成。类似的MxA介导的病毒核衣壳蛋白的再分布与其他布尼亚病毒，如布尼亚韦拉病毒和裂谷热病毒检测。MxA（E645R）是MxA的羧基端突变体，对LACV没有抗病毒活性，但不导致复合物的形成。野生型MxA，但不是MxA（E645R），能够结合LACV核衣壳蛋白在免疫共沉淀试验，证明了MxA的羧基末端效应域的重要性。这些结果说明了一种有效的IFN作用机制，即一种必需的病毒成分被困在细胞质内含物中，而不能用于产生新的病毒颗粒。
Bunyaviruses replicate in the cytoplasm of infected cells. New viral particles are formed by budding of nucleocapsids into the Golgi apparatus. We have previously shown that the IFN-induced human MxA protein inhibits bunyavirus replication by an unknown mechanism. Here we demonstrate that MxA binds to the nucleocapsid protein of La Crosse virus (LACV) and colocalizes with the viral protein in cytoplasmic complexes. Electron microscopy revealed that these complexes accumulated in the perinuclear area and consisted of highly ordered fibrillary structures. A similar MxA-mediated redistribution of viral nucleocapsid proteins was detected with other bunyaviruses, such as Bunyamwera virus and Rift Valley fever virus. MxA(E645R), a carboxy-terminal mutant of MxA without antiviral activity against LACV, did not lead to complex formation. Wild-type MxA, but not MxA(E645R), was able to bind to LACV nucleocapsid protein in coimmunoprecipitation assays, demonstrating the importance of the carboxy-terminal effector domain of MxA. These results illustrate an efficient mechanism of IFN action whereby an essential virus component is trapped in cytoplasmic inclusion sand becomes unavailable for the generation of new virus particles.