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J Virol. 2015 Aug 19. pii: JVI.01744-15. [Epub ahead of print]
Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses.
Verhelst J1, Spitaels J1, N?rnberger C2, De Vlieger D1, Ysenbaert T1, Staeheli P3, Fiers W1, Saelens X4.
Author information
Abstract
The interferon-induced Mx1 gene is an important part of the mammalian defense against influenza viruses. Mus musculus Mx1 inhibits influenza A 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, over half of which are present in the GTPase domain and two in loop L4. However, the in vitro GTPase activity of Mx1 from the two mouse species was similar. Replacing one of the residues in loop L4 in M. spretus Mx1 by the corresponding residue of A2G Mx1 increased its antiviral activity. We also show that deletion of loop L4 prevented binding of Mx1 to influenza A virus nucleoprotein and hence abolished antiviral activity of mouse Mx1. These results indicate that loop L4 of mouse Mx1 is a determinant of antiviral activity. Our findings suggest that Mx proteins from different mammals use a common mechanism to inhibit influenza A viruses.
IMPORTANCE:
Mx proteins are evolutionary conserved in vertebrates and inhibit a wide range of viruses. Still, the exact details of their antiviral mechanisms remain largely unknown. Functional comparison of Mx genes from two species, that diverged relatively recently in evolution, can provide novel insight into these mechanisms. We show that both Mus musculus A2G Mx1 and Mus spretus Mx1 target influenza nucleoprotein. We also found that loop L4 in mouse Mx1 is crucial for its antiviral activity, as was reported recently for primate MxA. This indicates that human and mouse Mx proteins, which diverged by 75 million years of evolution, recognize and inhibit influenza A viruses by a common mechanism.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26292322 [PubMed - as supplied by publisher]
Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses.
Verhelst J1, Spitaels J1, N?rnberger C2, De Vlieger D1, Ysenbaert T1, Staeheli P3, Fiers W1, Saelens X4.
Author information
Abstract
The interferon-induced Mx1 gene is an important part of the mammalian defense against influenza viruses. Mus musculus Mx1 inhibits influenza A 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, over half of which are present in the GTPase domain and two in loop L4. However, the in vitro GTPase activity of Mx1 from the two mouse species was similar. Replacing one of the residues in loop L4 in M. spretus Mx1 by the corresponding residue of A2G Mx1 increased its antiviral activity. We also show that deletion of loop L4 prevented binding of Mx1 to influenza A virus nucleoprotein and hence abolished antiviral activity of mouse Mx1. These results indicate that loop L4 of mouse Mx1 is a determinant of antiviral activity. Our findings suggest that Mx proteins from different mammals use a common mechanism to inhibit influenza A viruses.
IMPORTANCE:
Mx proteins are evolutionary conserved in vertebrates and inhibit a wide range of viruses. Still, the exact details of their antiviral mechanisms remain largely unknown. Functional comparison of Mx genes from two species, that diverged relatively recently in evolution, can provide novel insight into these mechanisms. We show that both Mus musculus A2G Mx1 and Mus spretus Mx1 target influenza nucleoprotein. We also found that loop L4 in mouse Mx1 is crucial for its antiviral activity, as was reported recently for primate MxA. This indicates that human and mouse Mx proteins, which diverged by 75 million years of evolution, recognize and inhibit influenza A viruses by a common mechanism.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26292322 [PubMed - as supplied by publisher]