The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses
- Hannover Medical School, Germany
- Technical University of Munich, Germany
- University of Freiburg, Germany
- Princeton University, United States
- University of Oxford, United Kingdom
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.
Data availability
The raw datasets produced in this study are available at PRIDE (PXD028276; http://www.ebi.ac.uk/pride). The dataset analyses and the raw bottling images are included in the Supplementary Files 1-3 and in the Source Data folder, respectively.
Article and author information
Author details
Funding
Horizon 2020 Framework Programme (H2020-EU.1.3.1)
- Jan Rehwinkel
- Andreas Pichlmair
- Beate Sodeik
Medical Research Council
- Jan Rehwinkel
National Institutes of Health (NIGMS,GM114141)
- Ileana M Cristea
European Research Council (ERC-CoG ProDAP 817798)
- Andreas Pichlmair
Deutsche Forschungsgemeinschaft (PI1084/3,PI1084/4,PI1084/5,TRR179,and TRR237)
- Andreas Pichlmair
Deutsche Forschungsgemeinschaft (KO1579/13)
- Georg Kochs
Deutsche Forschungsgemeinschaft (CRC900 C2 158989968,EXC62 REBIRTH 24102914,EXC2155 RESIST 390874280,SO403/6)
- Beate Sodeik
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Adam P Geballe, Fred Hutchinson Cancer Research Center, United States
Version history
- Received: January 5, 2022
- Preprint posted: January 27, 2022 (view preprint)
- Accepted: April 22, 2022
- Accepted Manuscript published: April 27, 2022 (version 1)
- Version of Record published: May 30, 2022 (version 2)
Copyright
© 2022, Serrero et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses
eLife 11:e76804.
https://doi.org/10.7554/eLife.76804
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