Animal Models to Study Influenza Virus Pathogenesis and Control

Abstract

Influenza A virus causes a highly contagious respiratory disease with potentially fatal outcomes in both humans and animals. Animal models for studying the pathogenesis of the influenza virus are of considerable importance, both for practical treatments of the disease and for the development of vaccines to prevent it. Ideal animal models that accurately reflect the disease, respond to antiviral therapy, and induce a protective immune response to influenza infection or vacci- nation are important for advances in research. In the veterinary field, natural hosts can be utilized, although the application of vaccine and antiviral therapy in animals should be considered carefully because of the possible latency of viral infec- tion and acceleration of viral mutations. In a laboratory setting, ferrets have been used extensively in influenza research because the pathogenesis of the influenza virus in ferrets is very similar to that observed in humans. Contact ferret models have also been used to evaluate transmissibility of the influenza virus in humans in order to determine the pandemic potential. Laboratory mice are also experimentally infected with the influenza virus, although mice are not naturally infected and usually do not cause lethal disease without adaptation of the virus. Recently, cotton rat as a small animal model has proved useful because, as adaptation to human influenza strains is not required for the virus to replicate in the lower respiratory tract, subsequent disease develops. Non-human primates such as rhesus and cynomolgus macaques can be experimentally infected with the influenza virus and can become ill. Although the use of this model is limited, influenza models in non-human primates may be more predictive of the responses in humans due to their close evolution- ary relationship. In this review, we will discuss the characteristics of these species as a potential influenza model. We will also highlight data obtained from animal models that are expected to contribute to the development of vaccines and treatments to improve the lives of both humans and animals from infection in the future.