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
PubMed Central IDPMC9150894
Grant ListMC_UU_00008/8 / MRC_ / Medical Research Council / United Kingdom
R01 GM114141 / GM / NIGMS NIH HHS / United States