The antiviral GTPase MxB is packaged into virions and binds via its N-terminal domain to alphaherpesvirus capsids

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Abstract
The interferon-inducible myxovirus resistance proteins (Mx) belong to the dynamin-like GTPases; MxA is a restriction factor against several RNA viruses, while MxB restricts infections of lentiviruses and herpesviruses. Humans express MxA(1–662) with an N-terminal domain (NTD) of 43 residues, MxB(1–715) with an NTD of 91 residues, and a truncated MxB(26–715) with an NTD of 66 residues. Although the roles of the GTPase and stalk domains during infection are increasingly being elucidated, the functions of the different NTDs remain poorly understood. Using cell lines stably expressing Mx proteins, we show that MxB(1–715), but not MxA, inhibited infection by herpes simplex virus (HSV-1) and pseudorabies virus (PrV). Quantitative mass spectrometry and subviral fractionation experiments indicate that MxB(1–715), but not the truncated MxB(26–715) or MxA(1–662), was enriched in the tegument of HSV-1 and PrV virions. Moreover, dimeric, recombinant, chimeric proteins with the NTD peptides MxB(1–91) or MxB(1–35), and to a lesser extent MxB(26–91), bound to tegumented HSV-1 capsids, while MxA(1–43) did not. In contrast, de-tegumented HSV-1 and PrV capsids bound to proteins with MxB(1–91), but not to those with MxB(1–35) or MxA(1–43). Our findings indicate that the NTD of MxB is crucial to restrict HSV-1 and PrV infections, that newly assembled virions package MxB into the tegument around the capsid, and that both the N-terminal MxB amino acid residues 1–25 and 26–91 contribute to its binding to tegumented and de-tegumented herpesviral capsids.
Funding Information
  • Deutsche Forschungsgemeinschaft (SO403/6 grant 443889136)
  • Deutsche Forschungsgemeinschaft (CRC900 C2 grant 158989968)
  • Deutsche Forschungsgemeinschaft (EXC2155 RESIST grant 390874280)
  • Horizon 2020 Framework Programme (H2020-EU.1.3.1, #675,278; Marie-Curie Actions ITN-EDGE)
  • Deutsches Zentrum für Infektionsforschung (DZIF, TTU 07.826_00)
  • Deutsche Forschungsgemeinschaft (KO1579/13-1 grant 443889136)
  • Deutsche Forschungsgemeinschaft (SCHW632/25-1 grant 505474100)
  • Deutsche Forschungsgemeinschaft (BO5917/4-1 grant 576180008)
  • Hannover Biomedical Research School
  • Center for Infection Biology

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