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Enhanced virus resistance of transgenic mice expressing the human MxA protein
J Pavlovic1, H A Arzet, H P Hefti
1Institut für Medizinische Virologie, Universität Zürich, Switzerland.
Abstract:
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.
Insights
MxA protein provides strong antiviral defense in vivo. Transgenic mice expressing MxA showed resistance to RNA viruses like influenza, demonstrating its potential to protect humans from viral infections.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- MxA is an interferon-induced GTPase known for its antiviral properties.
- MxA expression confers resistance to various RNA viruses in cell culture.
Purpose of the Study:
- To evaluate the in vivo antiviral efficacy of MxA.
- To generate and characterize MxA-expressing transgenic mice.
Main Methods:
- Generation of transgenic mice expressing MxA cDNA under a constitutive promoter.
- Assessment of viral susceptibility in MxA-expressing embryonic fibroblasts.
- Challenging transgenic mice with Thogoto, influenza A, and vesicular stomatitis viruses.
Main Results:
- MxA-expressing fibroblasts showed reduced susceptibility to Thogoto, influenza A, and vesicular stomatitis viruses.
- Transgenic mice exhibited increased survival rates after challenge with Thogoto virus.
- Transgenic mice demonstrated enhanced resistance to intracerebral influenza A and vesicular stomatitis virus infections.
Conclusions:
- MxA is a potent antiviral agent in vivo.
- MxA confers significant protection against RNA virus infections in a whole-organism model.
- MxA holds potential for therapeutic applications against viral pathogens in humans.