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Journal of Virology, April 2009, p. 3843-3851, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02453-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Intranasal Administration of Alpha Interferon Reduces Seasonal Influenza A Virus Morbidity in Ferrets

Daniela Kugel,¹ Georg Kochs,¹ Karola Obojes,⁶ Joachim Roth,² Gary P. Kobinger,^3,5 Darwyn Kobasa,^4,5 Otto Haller,¹ Peter Staeheli,¹ and Veronika von Messling^6*

Department of Virology, University of Freiburg, Freiburg, Germany,¹ Institute for Veterinary Physiology, University of Giessen, Giessen, Germany,² Special Pathogens Program,³ Respiratory Viruses Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada,⁴ Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada,⁵ INRS-Institut Armand-Frappier, University of Quebec, Montreal, Quebec, Canada⁶

Received 28 November 2008/ Accepted 23 January 2009

The type I interferon (IFN) response represents one of the first lines of defense against influenza virus infections. In this study, we assessed the protective potential of exogenous IFN- against seasonal and highly pathogenic influenza viruses in ferrets. Intranasal treatment with IFN- several hours before infection with the H1N1 influenza A virus strain A/USSR/90/77 reduced viral titers in nasal washes at least 100-fold compared to mock-treated controls. IFN-treated animals developed only mild and transient respiratory symptoms, and the characteristic fever peak seen in mock-treated ferrets 2 days after infection was not observed. Repeated application of IFN- substantially increased the protective effect of the cytokine treatment. IFN- did not increase survival after infection with the highly pathogenic H5N1 avian influenza A virus strain A/Vietnam/1203/2004. However, viral titers in nasal washes were significantly reduced at days 1 and 3 postinfection. Our study shows that intranasal application of IFN- can protect ferrets from seasonal influenza viruses, which replicate mainly in the upper respiratory tract, but not from highly pathogenic influenza viruses, which also disseminate to the lung. Based on these results, a more intensive evaluation of IFN- as an emergency drug against pandemic influenza A is warranted.

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* Corresponding author. Mailing address: INRS-Institut Armand-Frappier, University of Quebec, 531 boul. des Prairies, Laval, Quebec H7V 1B7, Canada. Phone: (450) 687 5010. Fax: (450) 686 5305. E-mail: veronika.vonmessling{at}iaf.inrs.ca

Published ahead of print on 4 February 2009.

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Journal of Virology, April 2009, p. 3843-3851, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02453-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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