A mouse model of chikungunya virus-induced musculoskeletal inflammatory disease: evidence of arthritis, tenosynovitis, myositis, and persistence

Autor(es): Morrison Thomas E, Oko Lauren, Montgomery Stephanie A, Whitmore Alan C, Lotstein Alina R, Gunn Bronwyn M, Elmore Susan A, Heise Mark T


Resumo: 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, - infected travelers introduced CHIKV to new regions. The pathogenesis of CHIKV is poorly understood, - 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 - 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 - swelling of the inoculated limb. Histologic analysis of hind limb sections revealed severe necrotizing myositis, mixed inflammatory cell arthritis, chronic active tenosynovitis, - multifocal vasculitis. Interestingly, these disease signs - 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 - histopathologic findings that are consistent with the disease signs of CHIKV-infected humans, providing a useful tool for studying viral - host factors that drive CHIKV pathogenesis - for evaluating potential therapeutics against this emerging viral disease.


Imprenta: The American Journal of Pathology, v. 178, n. 1, p. 32-40, 2011


Identificador do objeto digital: 10.1016/j.ajpath.2010.11.018


Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever


Data de publicação: 2011