Abstract
MxA, a member of the dynamin superfamily, is a potent host restriction factor for influenza A virus replication. The viral nucleoprotein (NP) of influenza A virus has been suggested to be a target of MxA. However, the molecular details of the interactions between NP and MxA remain unknown. In the present study, loop L4 of MxA, which was shown to target viral component and is missing in the crystal structure of MxA was modeled on a dimer of the MxA. The dimer was then docked onto NP. The resulting NP-MxA dimer complex is in agreement with previous studies, as the interface contains many residues that were previously identified to be associated with MxA resistance. And the model was the used to construct NP-MxA ring. We also constructed a structural model of the complex of influenza virus NP and polymerase, and the NP residues that interact with MxA in the NP-MxA model partly overlap with those in the NP-polymerase model, so MxA may competitively inhibit the binding of NP and the polymerase and disrupt the assembly of ribonucleoprotein (RNP) complex. These results of this work represent a putative molecular mechanisms for MxA antiviral activity.
