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

Manutea C. Serrero, Virginie Girault, Sebastian Weigang, Todd M. Greco, Ana Ramos-Nascimento, Fenja Anderson, Antonio Piras, Ana Hickford Martinez, Jonny Hertzog, Anne Binz, Anja Pohlmann, Ute Prank, Jan Rehwinkel, Rudolf Bauerfeind, Ileana M. Cristea, Andreas Pichlmair, Georg Kochs, Beate Sodeik

Research output: Contribution to journalComment/debatepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere76804
JournaleLife
Volume11
DOIs
StatePublished - Apr 2022

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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