Limitations of Current in Vivo Mouse Models for the Study of Chikungunya Virus Pathogenesis

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes febrile chikungunya fever (CHIKF) in humans. This disease is debilitating and characterized by acute fever onset and chronic incapacitating polyarthralgia. CHIKF pathogenesis remains poorly defined with no approved vaccines and therapies. Recent outbreaks in the Caribbean islands have elevated concerns over the possibility of a global pandemic. Tremendous efforts have been made to develop relevant mouse models to enable the study of infection and immunity against this viral disease. Among them, the more common C57BL/6 mouse model demonstrated the ability to recapitulate the symptoms shown in infected humans, including self-limiting arthritis, myositis, and tenosynovitis. This has facilitated the unraveling of some key factors involved in disease pathogenesis of CHIKF. However, the stark differences in immune response between humans and mouse models necessitate the development of an animal model with an immune system that is more genetically similar to the human system for a better representation. In this paper, we aim to uncover the limitations of the C57BL/6 model and discuss alternative mouse models for CHIKV research.