@article{7bac429900964108a3cb551b8d6e09ca,
title = "The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses",
abstract = "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.",
author = "Serrero, {Manutea C.} and Virginie Girault and Sebastian Weigang and Greco, {Todd M.} and Ana Ramos-Nascimento and Fenja Anderson and Antonio Piras and Martinez, {Ana Hickford} and Jonny Hertzog and Anne Binz and Anja Pohlmann and Ute Prank and Jan Rehwinkel and Rudolf Bauerfeind and Cristea, {Ileana M.} and Andreas Pichlmair and Georg Kochs and Beate Sodeik",
note = "Funding Information: We thank Katinka D?hner and Franziska H?sers (Institute of Virology, Hannover Medical School) as well as Miriam Schilling (University of Oxford, UK) for many constructive discussions and feedback on the manuscript, and Jasper G?tting (Institute of Virology, Hannover Medical School) for support on bioinformatics analyses. We are grateful to Ari Helenius (ETH Z?rich, Switzerland), Graham Ogg (University of Oxford, UK), Gary Cohen (University of Pennsylvania, USA), Helena Browne (Cambridge University, UK), Jay Brown (University of Virginia, USA), Jeffrey Cohen (NIH, Bethesda, USA), Pat Spear (Northwestern Medical School, USA), and Roselyn Eisenberg (University of Pennsylvania, USA) for their generous donation of virus strains and invaluable antibodies. Our research was supported by the EU 7th framework (Marie-Curie Actions ITN-EDGE; https://ec.europa.eu/research/mariecurieactions/about/innovative-training-networks_en, H2020-EU.1.3.1, #675278 to JR, AP, and BS), the UK MRC (core funding of theMedical Research Council Human Immunology Unit to JR), the NIH (NIGMS, GM114141 to IMC), an EU ERC consolidator grant (ERC-CoG ProDAP 817798 to AP), and the German Research Foundation (http://www.dfg.de/; PI1084/3, PI1084/4, PI1084/5, TRR179, and TRR237 to AP; KO1579/13 to GK; CRC900 C2 158989968, EXC62 REBIRTH 24102914, EXC2155 RESIST 390874280, SO403/6 to BS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: ? Our research was supported by the EU Publisher Copyright: {\textcopyright} 2022, eLife Sciences Publications Ltd. All rights reserved.",
year = "2022",
month = apr,
doi = "10.7554/eLife.76804",
language = "English (US)",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}