ID: 208: Comparison of the antiviral activity of Mus spretus Mx1 and Mus musculus A2G Mx1 against influenza A viruses

Abstract

The interferon-induced Mx1 gene is an important part of the mammalian defense against influenza viruses. Mouse Mx1 inhibits influenza virus replication and transcription by suppressing the polymerase activity of viral ribonucleoproteins (vRNPs). Here, we compared the anti-influenza activity of Mx1 from Mus musculus A2G with its ortholog from Mus spretus . We found that the antiviral activity of M. spretus Mx1 was less potent than that of M. musculus Mx1. Sequence comparison of M. musculus with M. spretus Mx1 revealed 25 amino acid differences, half of which are present in the GTPase domain. However, no differences in GTPase activity could be detected. In addition, 2 differences are present in loop L4. Replacing one of these residues in M. spretus Mx1 by the corresponding residue of A2G Mx1 increased its antiviral activity. We also show that deletion of loop L4 prevented NP binding and hence abolished antiviral activity of mouse Mx1. Taken together, these results indicate that loop L4 of mouse Mx1 is an important determinant of antiviral activity, similar to its human homolog MxA. Our findings suggest that Mx proteins from different mammals use a common mechanism to inhibit influenza A viruses.