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Journal of Virology, February 2007, p. 2025-2030, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.01718-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protective Role of Beta Interferon in Host Defense against Influenza A Virus{triangledown}

Iris Koerner,1 Georg Kochs,1 Ulrich Kalinke,2 Siegfried Weiss,3 and Peter Staeheli1*

Department of Virology, University of Freiburg, 79104 Freiburg, Germany,1 Division of Immunology, Paul-Ehrlich-Institut, Langen, 63225 Langen, Germany,2 Molekulare Immunologie, Helmholtz Zentrum für Infektionsforschung, 38124 Braunschweig, Germany3

Received 8 August 2006/ Accepted 20 November 2006

Type I interferon (IFN), which includes the IFN-{alpha} and -ß subtypes, plays an essential role in host defense against influenza A virus. However, the relative contribution of IFN-ß remains unresolved. In mice, type I IFN is effective against influenza viruses only if the IFN-induced resistance factor Mx1 is present, though most inbred mouse strains, including the recently developed IFN-ß-deficient mice, bear only defective Mx1 alleles. We therefore generated IFN-ß-deficient mice carrying functional Mx1 alleles (designated Mx-BKO) and compared them to either wild-type mice bearing functional copies of both IFN-ß and Mx1 (designated Mx-wt) or mice carrying functional Mx1 alleles but lacking functional type I IFN receptors (designated Mx-IFNAR). Influenza A virus strain SC35M (H7N7) grew to high titers and readily formed plaques in monolayers of Mx-BKO and Mx-IFNAR embryo fibroblasts which showed no spontaneous expression of Mx1. In contrast, Mx-wt embryo fibroblasts were found to constitutively express Mx1, most likely explaining why SC35M did not grow to high titers and formed no visible plaques in such cells. In vivo challenge experiments in which SC35M was applied via the intranasal route showed that the 50% lethal dose was about 20-fold lower in Mx-BKO mice than in Mx-wt mice and that virus titers in the lungs were increased in Mx-BKO mice. The resistance of Mx-BKO mice to influenza A virus strain PR/8/34 (H1N1) was also substantially reduced, demonstrating that IFN-ß plays an important role in the defense against influenza A virus that cannot be compensated for by IFN-{alpha}.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6579. Fax: 49-761-203-5350. E-mail: peter.staeheli{at}uniklinik-freiburg.de.

{triangledown} Published ahead of print on 6 December 2006.

Journal of Virology, February 2007, p. 2025-2030, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.01718-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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