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

eLife

Andreas Pichlmair¹  Jan Rehwinkel¹  Virginie Girault²  Ileana M Cristea²  Ute Prank²  Ana Ramos-Nascimento³  Todd M Greco⁴  Georg Kochs⁵  Fenja Anderson⁵  Jonny Hertzog⁵  Antonio Piras⁵  Anja Pohlmann⁵  Manutea C Serrero⁵  Rudolf Bauerfeind⁵  Ana Hickford Martinez⁶  Sebastian Weigang⁶  Anne Binz⁷  Beate Sodeik⁷ 

[1] German Center for Infection Research (DZIF), Hannover-Braunschweig Partner Site, Hannover, Germany;RESIST - Cluster of Excellence, Hannover Medical School, Hannover, Germany;Department of Molecular Biology, Princeton University, Princeton, United States;Institute of Virology, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany;Institute of Virology, Hannover Medical School, Hannover, Germany;Institute of Virology, Technical University Munich, Munich, Germany;MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom;

关键词: MxB;    herpes simplex virus;    interferon;    GTPase;    capsid;    Mx2;   

DOI  :  10.7554/eLife.76804

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown