Small animal models for studying filovirus pathogenesis

Filovirus small animal disease models have so far been developed in laboratory mice, guinea pigs, and hamsters. Since immunocompetent rodents do not exhibit overt signs of disease following infection with wild-type filoviruses isolated from humans, rodent models have been established using adapted viruses produced through sequential passage in rodents. Rodent-adapted viruses target the same cells/tissues as the wild-type viruses, making rodents invaluable basic research tools for studying filovirus pathogenesis. Moreover, comparative analyses using wild-type and rodent-adapted viruses have provided beneficial insights into the molecular mechanisms of pathogenicity and acquisition of species-specific virulence. Additionally, wild-type filovirus infections in immunodeficient rodents have provided a better understanding of the host factors required for resistance to filovirus infection and of the immune response against the infection. This chapter provides comprehensive information on the filovirus rodent models and rodent-adapted filoviruses. Specifically, we summarize the clinical and pathological features of filovirus infections in all rodent models described to date, including the recently developed humanized and collaborative cross (CC) resource recombinant inbred (RI) intercrossed (CC-RIX) mouse models. We also cover the molecular determinants responsible for adaptation and virulence acquisition in a number of rodent-adapted filoviruses. This chapter clearly defines the characteristic and advantages/disadvantages of rodent models, helping to evaluate the practical use of rodent models in future filovirus studies.