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

ABSTRACT: The interferon-inducible myxovirus resistance proteins belong to the dynamin-like GTPases, with MxA being 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 elucidated, the function of the different NTDs is not fully understood. Using cell lines stably expressing Mx proteins, we show in multi-step growth curves at low multiplicity of infection that MxB(1-715) and, less so, MxB(26-715) and MxA inhibited infection with herpes simplex virus (HSV-1), while MxB(1-715) and MxB(25-715) restricted pseudorabies virus (PrV) to a similar extent. Quantitative mass spectrometry and subviral fractionation experiments indicate that MxB(1-715), but not MxB(26-715) or MxA(1-662), enriched with the tegument of HSV-1 and PrV virions.. Moreover, we generated recombinant proteins with different NTDs and showed that MxB(1-91), MxB(1-35), and to a lesser extent MxB(26-91) bound to isolated HSV-1 capsids, while MxA(1-43) did not. 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 the N-terminal and the C-terminal part of the MxB-NTD contribute to its binding to herpesviral capsids.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Herpes Simplex

SUBMITTER: Boris Bogdanow  

LAB HEAD: Fan Liu

PROVIDER: PXD069031 | Pride | 2026-06-30

REPOSITORIES: Pride