The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses.

TitleThe interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses.
Publication TypeJournal Article
Year of Publication2022
AuthorsSerrero, MC, Girault, V, Weigang, S, Greco, TM, Ramos-Nascimento, A, Anderson, F, Piras, A, Martinez, AHickford, Hertzog, J, Binz, A, Pohlmann, A, Prank, U, Rehwinkel, J, Bauerfeind, R, Cristea, IM, Pichlmair, A, Kochs, G, Sodeik, B
JournalElife
Volume11
Date Published2022 Apr 27
ISSN2050-084X
KeywordsCapsid, Capsid Proteins, GTP Phosphohydrolases, Herpesviridae, Interferons, Simplexvirus
Abstract

<p>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.</p>

DOI10.7554/eLife.76804
Alternate JournalElife
PubMed ID35475759
Grant ListCRC900 C2 158989968,EXC62 REBIRTH 24102914,EXC2155 RESIST 390874280,SO403/6 / / Deutsche Forschungsgemeinschaft /
MC_UU_00008/8 / MRC_ / Medical Research Council / United Kingdom
KO1579/13 / / Deutsche Forschungsgemeinschaft /
NIGMS,GM114141 / NH / NIH HHS / United States
PI1084/3,PI1084/4,PI1084/5,TRR179,and TRR237 / / Deutsche Forschungsgemeinschaft /
H2020-EU.1.3.1 / / Horizon 2020 Framework Programme /
MC_UU_00008/8 / MRC_ / Medical Research Council / United Kingdom
NIGMS, GM114141 / NH / NIH HHS / United States
ERC-CoG ProDAP 817798 / ERC_ / European Research Council / International
PI1084/3 / / Deutsche Forschungsgemeinschaft /
PI1084/4 / / Deutsche Forschungsgemeinschaft /
PI1084/5 / / Deutsche Forschungsgemeinschaft /
TRR179/TP11 / / Deutsche Forschungsgemeinschaft /
TRR237/A07 / / Deutsche Forschungsgemeinschaft /
KO1579/13-1 / / Deutsche Forschungsgemeinschaft /
CRC900 C2, 158989968 / / Deutsche Forschungsgemeinschaft /
EXC62 REBIRTH, 24102914 / / Deutsche Forschungsgemeinschaft /
EXC2155 RESIST, 390874280 / / Deutsche Forschungsgemeinschaft /
SO403/6, 443889136 / / Deutsche Forschungsgemeinschaft /
TTU 07.826_00 / / Deutsches Zentrum für Infektionsforschung /