A consideration of animal models used for study of influenza virus inhibitors

Abstract

When an animal model is sought for the study of potential anti-influenza virus agents, investigators commonly turn to the mouse or ferret, which can be experimentally infected by the virus. The ferret will develop febrile illness when infected with influenza A viruses and has successfully been used for study of influenza virus inhibitors. Evaluation parameters commonly include temperature elevation, virus recovery from respiratory tissues and nasal washes and pneumonia-associated mortality. The mouse is often chosen because of its lower cost, ready availability, and ease of handling. Disease parameters using this model include pneumonia-associated mortality, decline in arterial oxygen saturation, lung consolidation, lung virus titers, host weight loss, and increase in serum (α 1-acid glycoprotein. Antiviral data using both animal models are usually comparable; based on studies with amantadine, rimantadine, zanamivir, and oseltamivir, they are predictive for efficacy in the clinic. Rapid development of viral resistance to amantadine and rimantadine and a failure to observe resistance development to the influenza neuraminidase inhibitors has been demonstrated in the murine model. Immunocompromised mice have been used in studies with the latter compounds to demonstrate that their disease-inhibitory effect is not dependent upon the host's immune system. The concepts in the utilization of animal models for study of antiviral drugs will be reviewed.