Methods for Evaluation of Antiviral Efficacy Against Influenza Virus Infections in Animal Models
Compounds undergoing preclinical development for anti-influenza virus activity require evaluation in small animal models. Laboratory mice are most commonly used for initial studies because of size, cost, and availability. Cotton rats, guinea pigs, and ferrets (particularly) have been used for more advanced studies. Each animal infection model has certain limitations relative to human influenza infections. For example, the fever response that is evident in humans only occurs with consistency in ferrets. Mice infected with mouse-adapted viruses and ferrets infected with highly pathogenic avian influenza viruses suffer severe disease, whereas cotton rats and guinea pigs manifest few symptoms. Thus, for each animal model there is a certain set of disease parameters that can be measured. Here we describe methods for assessing the efficacy of anti-influenza virus compounds in each of these animal species.
Key wordsInfluenza Antiviral Mice Cotton rats Guinea pigs Ferrets
This work was funded in part with Federal funds from the Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201000039I/HHSN27200005/A37.
- 14.Ryan DM, Ticehurst J, Dempsey MH, Penn CR (1994) Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase). Antimicrob Agents Chemother 38:2270–2275PubMedCrossRefGoogle Scholar
- 25.Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Hyg 27:493–498Google Scholar
- 45.Motulsky H (1995) Comparing two proportions. In: Motulsky H (ed) Intuitive biostatistics. Oxford University Press, New York, pp 235–236Google Scholar