Short communication
A Mouse Model of Chikungunya Virus–Induced Musculoskeletal Inflammatory Disease: Evidence of Arthritis, Tenosynovitis, Myositis, and Persistence

https://doi.org/10.1016/j.ajpath.2010.11.018Get rights and content
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Chikungunya virus (CHIKV), an emerging mosquito-borne Alphavirus, causes debilitating rheumatic disease in humans that can last for weeks to months. Starting in 2004, a CHIKV outbreak in the Indian Ocean region affected millions of people, and infected travelers introduced CHIKV to new regions. The pathogenesis of CHIKV is poorly understood, and no approved vaccines or specific therapies exist. A major challenge to the study of CHIKV disease is the lack of a small animal model that recapitulates the major outcomes of human infection. In this study, the pathogenesis of CHIKV in C57BL/6J mice was investigated using biological and molecular clones of CHIKV isolated from human serum (CHIKV SL15649). After 14-day-old mice were inoculated with CHIKV SL15649 in the footpad, they displayed reduced weight gain and swelling of the inoculated limb. Histologic analysis of hind limb sections revealed severe necrotizing myositis, mixed inflammatory cell arthritis, chronic active tenosynovitis, and multifocal vasculitis. Interestingly, these disease signs and viral RNA persisted in musculoskeletal tissues for at least 3 weeks after inoculation. This work demonstrates the development of a mouse model of CHIKV infection with clinical manifestations and histopathologic findings that are consistent with the disease signs of CHIKV-infected humans, providing a useful tool for studying viral and host factors that drive CHIKV pathogenesis and for evaluating potential therapeutics against this emerging viral disease.

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Supported by National Institutes of Health (NIH) research grant K22 AI079163 (T.E.M.), NIH research grants U54 AI 057157-07 (SERCEB Project 2.1) and 2 R01 AR 047190 (M.T.H.), and in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.