Pavlovic J, Arzet H A, Hefti H P, Frese M, Rost D, Ernst B, Kolb E, Staeheli P, Haller O
Institut für Medizinische Virologie, Universität Zürich, Switzerland.
J Virol. 1995 Jul;69(7):4506-10. doi: 10.1128/JVI.69.7.4506-4510.1995.
MxA is a GTPase that accumulates to high levels in the cytoplasm of interferon-treated human cells. Expression of MxA cDNA confers to transfected cell lines a high degree of resistance against several RNA viruses, including influenza, measles, vesicular stomatitis, and Thogoto viruses. We have now generated transgenic mice that express MxA cDNA in the brain and other organs under the control of a constitutive promoter. Embryonic fibroblasts derived from the transgenic mice were nonpermissive for Thogoto virus and showed reduced susceptibility for influenza A and vesicular stomatitis viruses. The transgenic animals survived challenges with high doses of Thogoto virus by the intracerebral or intraperitoneal route. Furthermore, the transgenic mice were more resistant than their nontransgenic littermates to intracerebral infections with influenza A and vesicular stomatitis viruses. These results demonstrate 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.
MxA是一种GTP酶，在经干扰素处理的人类细胞的细胞质中会积累到高水平。MxA cDNA的表达赋予转染细胞系对多种RNA病毒的高度抗性，这些病毒包括流感病毒、麻疹病毒、水疱性口炎病毒和托高托病毒。我们现已培育出在组成型启动子控制下在大脑和其他器官中表达MxA cDNA的转基因小鼠。源自转基因小鼠的胚胎成纤维细胞对托高托病毒不敏感，对甲型流感病毒和水疱性口炎病毒的敏感性也降低。转基因动物通过脑内或腹腔途径经高剂量托高托病毒攻击后存活下来。此外，转基因小鼠比其非转基因同窝小鼠对甲型流感病毒和水疱性口炎病毒的脑内感染更具抗性。这些结果表明，MxA在体内是一种强大的抗病毒剂，这表明它可能保护人类免受某些病毒病原体感染的有害影响。
