Table 2.

Frequently used animal models of Chikungunya disease.

Model organism	Advantages	Disadvantages
Neonate mice	• Small animal model (size, generation time, handling, cost, etc.) • Large body of literature, availability of tools and reagents • Transgenic animals • Replicates high viremia and dissemination to multiple organs	• Evolutionary distance • Immunocompromised • Lethal model with limited time window for analysis
IFNI signaling deficient-mice (e.g., IFNAR1−/−, IFNAR1−/−, IFNGR1−/−)	• Small animal model (size, generation time, handling, cost, etc.) • Large body of literature, availability of tools and reagents • Transgenic animals • Replicates high viremia and dissemination to multiple organs	• Evolutionary distance • Immunocompromised • Lethal model with limited time window for analysis
Footpad swelling in wild-type mice	• Small animal model (size, generation time, handling, cost, etc.) • Large body of literature, availability of tools and reagents • Transgenic animals • Replicates viremia, dissemination to tissues and joints close to injection site and selected organs, arthritis-like disease and viral persistence • Non-lethal	• Evolutionary distance • Fails to replicate dissemination to all organs affected in human disease • Joint involvement unilateral
NHP (Rhesus macaques, Cynomolgus macaques)	• Evolutionary proximity—Similar physiology and immune response • Natural host • Replicates viremia, spread to organs and joints, fever, viral persistence, rashes, changes in blood biochemistry and CBC, cytokine, and chemokine response • Replicates joint involvement at very high challenge doses • Non-lethal	• Large animal model (size, generation time, handling, cost, etc.) • Ethical constraints of using primates in research • Replicates joint pathologies only at non-physiological challenge doses