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Murine Mx1 protein is an interferon-inducible GTPase which localizes in nuclei and inhibits influenza virus infection. Wild-type Mx1 and two mutant Mx1 proteins, each carrying a single mutation either in the GTP-binding motif (S50I) or in the self-assembly motif (C71S), were expressed in MDCK cells. Wild-type Mx1 localized in nuclei, forming small granules with minute dots, and inhibited influenza virus growth. Mutant S50I, which had no GTP-binding or GTPase activities, formed linear structures in nuclei and lacked anti-viral activity, while C71S appeared diffuse in nuclei as minute dots without granules, but retained the inhibitory activity against influenza virus growth. A correlation existed between GTPase activity, intranuclear distribution and antiviral activity. We concluded that GTPase activity is essential for expression of the biological activity of Mx1 protein.

Role of GTPase activity of murine Mx1 protein in nuclear localization and anti-influenza virus activity