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Title: Pathogenesis of the 1918 pandemic and H5N1 influenza virus infection in a guinea pig model: The antiviral potential of exogenous alpha-interferon to reduce virus shedding

Author
item VAN HOEVEN, NEAL - CDC, ATLANTA, GA
item BELSER, JESSICA - CDC, ATLANTA, GA
item SZRETTER, KRISTY - CDC, ATLANTA, GA
item STAEHELI, PETER - UNIV OF FREIBERG, GERMANY
item Swayne, David
item KATZ, JACQUELINE - CDC, ATLANTA, GA
item TUMPEY, TERRENCE - CDC, ATLANTA, GA

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/2009
Publication Date: 4/1/2009
Citation: Van Hoeven, N., Belser, J.A., Szretter, K.J., Staeheli, P., Swayne, D.E., Katz, J.M., Tumpey, T.M. 2009. Pathogenesis of the 1918 pandemic and H5N1 influenza virus infection in a guinea pig model: The antiviral potential of exogenous alpha-interferon to reduce virus shedding. Journal of Virology. 83(7):2851-2861.

Interpretive Summary: Small animal models are needed to study the effects of new and existing drugs for the treatment of deadly influenza virus infections. A guinea pig model was used to study the effect of alpha-interferon on avian and human influenza A virus infections. Intranasal exposure of guinea pigs to four avian and human influenza viruses produced infection. Virus was shed from the nose and was present in the lungs, but the infections did not produce disease. Intranasal treatment with human alpha interferon dramatically reduced influenza virus growth. The guinea pig may serve as a useful small-animal model for testing the effectiveness of anti-influenza drugs.

Technical Abstract: Although highly pathogenic avian influenza H5N1 viruses have yet to acquire the ability to transmit efficiently among humans, the geographic expansion, and continued outbreaks in humans and avian species underscore the need for more effective influenza vaccines and antivirals. Additional small animal models with which therapeutic approaches against virulent influenza viruses can be evaluated are needed. Here, 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 from nasal washes for up to five days post-inoculation and from lung tissue of all inoculated animals. However, other physiologic indicators normally associated with highly pathogenic influenza virus infection were absent in this species. We evaluated the ability of intranasal treatment with human alpha interferon (alphaIFN) to reduce lung and nasal wash titers in guinea pigs challenged with the reconstructed 1918 pandemic H1N1 virus or a clade 1 H5N1 virus. IFN treatment initiated one day prior to challenge significantly reduced or prevented infection of guinea pigs by both 1918 and H5N1 viruses, as measured by virus titer determination and post-inoculation seroconversion. We propose that the guinea pig may serve as a useful small-animal model for testing the efficacy of antiviral compounds and that alphaIFN treatment may be a useful antiviral strategy against highly virulent strains with pandemic potential.