MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
Anne Binz
Institute of Virology, Hannover Medical School, Hannover, Germany; RESIST - Cluster of Excellence, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Partner Site, Hannover, Germany
Anja Pohlmann
Institute of Virology, Hannover Medical School, Hannover, Germany; RESIST - Cluster of Excellence, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Partner Site, Hannover, Germany
Ute Prank
Institute of Virology, Hannover Medical School, Hannover, Germany
Jan Rehwinkel
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
Rudolf Bauerfeind
Research Core Unit Laser Microscopy, Hannover Medical School, Hannover, Germany
Ileana M Cristea
Department of Molecular Biology, Princeton University, Princeton, United States
Institute of Virology, Hannover Medical School, Hannover, Germany; RESIST - Cluster of Excellence, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Partner Site, Hannover, Germany
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.
