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Journal of Virology, August 1999, p. 6984-6991, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human MxA Protein Protects Mice Lacking a Functional Alpha/Beta Interferon System against La Crosse Virus and Other Lethal Viral Infections

Hans Peter Hefti,1 Michael Frese,2 Heinrich Landis,1 Claudio Di Paolo,1 Adriano Aguzzi,3 Otto Haller,2 and Jovan Pavlovic1,*

Institute of Medical Virology1 and Institute of Neuropathology,3 University of Zürich, Zürich, Switzerland, and Department of Virology, University of Freiburg, D-79104 Freiburg, Germany2

Received 21 December 1998/Accepted 16 April 1999

The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-alpha /beta ). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the beta  subunit of the IFN-alpha /beta receptor (IFNAR-1-/- mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA-transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1-/- mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.

* Corresponding author. Mailing address: Institute of Medical Virology, University of Zürich, Gloriastrasse 30, CH-8028 Zürich, Switzerland. Phone: 41-1-634 26 56. Fax: 41-1-634 49 06. E-mail: pavlovic{at}immv.unizh.ch.

Journal of Virology, August 1999, p. 6984-6991, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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