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Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses

(2015) JOURNAL OF VIROLOGY. 89(21). p.10879-10890
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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 virus activity of Mx1 from Mus musculus A2G with that of its ortholog from Mus spretus. We found that the antiviral activity of M. spretus Mx1 was less potent than that of M. musculus Mx1. Comparison of the M. musculus Mx1 sequence with the M. spretus Mx1 sequence revealed 25 amino acid differences, over half of which were present in the GTPase domain and 2 of which were present in loop L4. However, the in vitro GTPase activity of Mx1 from the two mouse species was similar. Replacement of 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 the binding of Mx1 to influenza A virus nucleoprotein and, hence, abolished the 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.
Keywords
WILD MICE, IDENTIFICATION, INNATE IMMUNITY, RESISTANCE PROTEIN-A, GENE, VESICULAR STOMATITIS-VIRUS, BINDING, DOMAIN, OVEREXPRESSION, SENSITIVITY

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Chicago
Verhelst, Judith, Jan Spitaels, Cindy Nurnberger, Dorien De Vlieger, Tine Ysenbaert, Peter Staeheli, Walter Fiers, and Xavier Saelens. 2015. “Functional Comparison of Mx1 from Two Different Mouse Species Reveals the Involvement of Loop L4 in the Antiviral Activity Against Influenza A Viruses.” Journal of Virology 89 (21): 10879–10890.
APA
Verhelst, Judith, Spitaels, J., Nurnberger, C., De Vlieger, D., Ysenbaert, T., Staeheli, P., Fiers, W., et al. (2015). Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses. JOURNAL OF VIROLOGY, 89(21), 10879–10890.
Vancouver
1.
Verhelst J, Spitaels J, Nurnberger C, De Vlieger D, Ysenbaert T, Staeheli P, et al. Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses. JOURNAL OF VIROLOGY. 2015;89(21):10879–90.
MLA
Verhelst, Judith, Jan Spitaels, Cindy Nurnberger, et al. “Functional Comparison of Mx1 from Two Different Mouse Species Reveals the Involvement of Loop L4 in the Antiviral Activity Against Influenza A Viruses.” JOURNAL OF VIROLOGY 89.21 (2015): 10879–10890. Print.
@article{6981763,
  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 virus activity of Mx1 from Mus musculus A2G with that of its ortholog from Mus spretus. We found that the antiviral activity of M. spretus Mx1 was less potent than that of M. musculus Mx1. Comparison of the M. musculus Mx1 sequence with the M. spretus Mx1 sequence revealed 25 amino acid differences, over half of which were present in the GTPase domain and 2 of which were present in loop L4. However, the in vitro GTPase activity of Mx1 from the two mouse species was similar. Replacement of 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 the binding of Mx1 to influenza A virus nucleoprotein and, hence, abolished the 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.},
  author       = {Verhelst, Judith and Spitaels, Jan and Nurnberger, Cindy and De Vlieger, Dorien and Ysenbaert, Tine and Staeheli, Peter and Fiers, Walter and Saelens, Xavier},
  issn         = {0022-538X},
  journal      = {JOURNAL OF VIROLOGY},
  language     = {eng},
  number       = {21},
  pages        = {10879--10890},
  title        = {Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses},
  url          = {http://dx.doi.org/10.1128/JVI.01744-15},
  volume       = {89},
  year         = {2015},
}

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