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

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 res...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:eLife 2022-04, Vol.11
Hauptverfasser: Serrero, Manutea C, Girault, Virginie, Weigang, Sebastian, Greco, Todd M, Ramos-Nascimento, Ana, Anderson, Fenja, Piras, Antonio, Hickford Martinez, Ana, Hertzog, Jonny, Binz, Anne, Pohlmann, Anja, Prank, Ute, Rehwinkel, Jan, Bauerfeind, Rudolf, Cristea, Ileana M, Pichlmair, Andreas, Kochs, Georg, Sodeik, Beate
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.76804