ENHANCED VIRUS-RESISTANCE OF TRANSGENIC MICE EXPRESSING THE HUMAN MXAPROTEIN

MxA is a GTPase that accumulates to high levels in the cytoplasm of in terferon-treated human cells. Expression of MxA cDNA confers to transf ected cell lines a high degree of resistance against several RNA virus es, including influenza, measles, vesicular stomatitis, and Thogoto vi ruses. We have now generated transgenic mice that express MxA cDNA in the brain and other organs under the control of a constitutive promote r. Embryonic fibroblasts derived from the transgenic mice were nonperm issive for Thogoto virus and showed reduced susceptibility for influen za A and vesicular stomatitis viruses, The transgenic animals survived challenges with high doses of Thogoto virus by the intracerebral or i ntraperitoneal route. Furthermore, the transgenic mice were more resis tant than their nontransgenic littermates to intracerebral infections with influenza A and vesicular stomatitis viruses. These results demon strate that MxA is a powerful antiviral agent in vivo, indicating that it may protect humans from the deleterious effects of infections with certain viral pathogens.