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Journal of Virology, April 2009, p. 2851-2861, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02174-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding{triangledown}

Neal Van Hoeven,1 Jessica A. Belser,1,2 Kristy J. Szretter,1,{dagger} Hui Zeng,1 Peter Staeheli,3 David E. Swayne,4 Jacqueline M. Katz,1 and Terrence M. Tumpey1*

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,1 Department of Microbiology, Mount Sinai School of Medicine, New York, New York,2 Department of Virology, University of Freiburg, Freiburg, Germany,3 Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia4

Received 14 October 2008/ Accepted 30 December 2008

Although highly pathogenic avian influenza H5N1 viruses have yet to acquire the ability to transmit efficiently among humans, the increasing genetic diversity among these viruses and continued outbreaks in avian species underscore the need for more effective measures for the control and prevention of human H5N1 virus infection. Additional small animal models with which therapeutic approaches against virulent influenza viruses can be evaluated are needed. In this study, we used the guinea pig model to evaluate the relative virulence of selected avian and human influenza A viruses. We demonstrate that guinea pigs can be infected with avian and human influenza viruses, resulting in high titers of virus shedding in nasal washes for up to 5 days postinoculation (p.i.) and in lung tissue of inoculated animals. However, other physiologic indicators typically associated with virulent influenza virus strains were absent in this species. We evaluated the ability of intranasal treatment with human alpha interferon ({alpha}-IFN) to reduce lung and nasal wash titers in guinea pigs challenged with the reconstructed 1918 pandemic H1N1 virus or a contemporary H5N1 virus. IFN treatment initiated 1 day prior to challenge significantly reduced or prevented infection of guinea pigs by both viruses, as measured by virus titer determination and seroconversion. The expression of the antiviral Mx protein in lung tissue correlated with the reduction of virus titers. We propose that the guinea pig may serve as a useful small animal model for testing the efficacy of antiviral compounds and that {alpha}-IFN treatment may be a useful antiviral strategy against highly virulent strains with pandemic potential.

* Corresponding author. Mailing address: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, MS G-16, 1600 Clifton Rd. NE, Atlanta, GA 30333. Phone: (404) 639-5444. Fax: (404) 639-2350. E-mail: tft9{at}cdc.gov

{triangledown} Published ahead of print on 14 January 2009.

{dagger} Present address: Washington University, School of Medicine, Campus Box 8051, 660 S. Euclid, St. Louis, MO 63110.

Journal of Virology, April 2009, p. 2851-2861, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02174-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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