TY - JOUR TI - The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses AU - Serrero, Manutea C AU - Girault, Virginie AU - Weigang, Sebastian AU - Greco, Todd M AU - Ramos-Nascimento, Ana AU - Anderson, Fenja AU - Piras, Antonio AU - Hickford Martinez, Ana AU - Hertzog, Jonny AU - Binz, Anne AU - Pohlmann, Anja AU - Prank, Ute AU - Rehwinkel, Jan AU - Bauerfeind, Rudolf AU - Cristea, Ileana M AU - Pichlmair, Andreas AU - Kochs, Georg AU - Sodeik, Beate A2 - Geballe, Adam P A2 - Ojala, Päivi M VL - 11 PY - 2022 DA - 2022/04/27 SP - e76804 C1 - eLife 2022;11:e76804 DO - 10.7554/eLife.76804 UR - https://doi.org/10.7554/eLife.76804 AB - 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. KW - MxB KW - herpes simplex virus KW - interferon KW - GTPase KW - capsid KW - Mx2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -