Switch in antiviral specificity of a GTPase upon translocation from the cytoplasm to the nucleus.
The Mx2 protein of rats is a cytoplasmic GTPase that protects cells against vesicular stomatitis virus but not against influenza virus. Since vesicular stomatitis virus replicates in the cytoplasm and influenza virus replicates in the nucleus, it was possible that the antiviral specificity of rat Mx2 protein was determined solely by the protein's subcellular localization. Here, we found that, indeed, rat Mx2 protein lost its anti-vesicular stomatitis virus activity and gained anti-influenza virus activity when it was directed to the nucleus by way of a foreign nuclear-transport signal appended to its amino terminus. These data show that rat Mx2 protein possesses an antiviral activity that is revealed only when the protein is shuttled to the nucleus.
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
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Johannes
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Arnheiter
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Meier
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000187:drug effects*; D021382:Protein Sorting Signals; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*
D000998:Antiviral Agents; C579067:Mx2 protein, mouse; C579066:Mx2 protein, rat; D064547:Myxovirus Resistance Proteins; D021382:Protein Sorting Signals; D011506:Proteins; D019204:GTP-Binding Proteins