The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses
The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses
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干扰素诱导型 GTPase MxB 促进疱疹病毒衣壳解体和基因组释放
DOI：
10.1101/2022.01.25.477704
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发表时间：
2022
期刊：
影响因子：
7.7
通讯作者：
B. Sodeik
中科院分区：
文献类型：
--
作者：
Manutea C. Serrero;V. Girault;Sebastian Weigang;T. Greco;Ana Ramos;Fenja Anderson;A. Piras;A. Martinez;Jonny Hertzog;A. Binz;Anja Pohlmann;Ute Prank;J. Rehwinkel;R. Bauerfeind;I. Cristea;A. Pichlmair;G. Kochs;B. Sodeik
宿主蛋白感知病毒产物并诱导防御机制，特别是在免疫细胞中。利用无细胞分析和定量质谱法，我们确定了单纯疱疹病毒衣壳-宿主蛋白复合物的相互作用组，并鉴定了大动力蛋白样GT3粘病毒抗性蛋白B（Mx B）作为与衣壳相互作用的干扰素诱导蛋白。电子显微镜分析表明，含有MxB的胞质溶胶有显着的能力，拆卸的二十面体衣壳的单纯疱疹病毒和水痘带状疱疹病毒成连接的三角形面的平板。相比之下，MxB突变体无法水解GTP或二聚化，衣壳在细胞质中保持完整。我们的数据表明，MxB感疱疹病毒衣壳，介导其拆卸，从而限制了传入衣壳和/或后代衣壳的组装的核靶向的效率。由此产生的病毒基因组从衣壳的过早释放可能会增强DNA传感器的激活，从而放大先天免疫反应。
Host proteins sense viral products and induce defence mechanisms, particularly in immune cells. Using cell-free assays and quantitative mass spectrometry, we determined the interactome of capsid- host protein complexes of herpes simplex virus and identified the large dynamin-like GTPase myxovirus resistance protein B (MxB) as an interferon-inducible protein interacting with capsids. Electron microscopy analyses showed that cytosols containing MxB had the remarkable capability to disassemble the icosahedral capsids of herpes simplex viruses and varicella zoster virus into flat sheets of connected triangular faces. In contrast, capsids remained intact in cytosols with MxB mutants unable to hydrolyse GTP or to dimerize. Our data suggest that MxB senses herpesviral capsids, mediates their disassembly, and thereby restricts the efficiency of nuclear targeting of incoming capsids and/or the assembly of progeny capsids. The resulting premature release of viral genomes from capsids may enhance the activation of DNA sensors, and thereby amplify the innate immune responses.
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
影响因子：
14.9
作者：
Kanehisa, M;Goto, S
通讯作者：
Goto, S