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.