Chikungunya virus arthritis in adult wild-type mice
Autor(es): Gardner Joy, Anraku Itaru, Le Thuy T, Larcher Thibaut, Major Lee, Roques Pierre, Schroder Wayne A, Higgs Stephen, Suhrbier Andreas
Resumo: Chikungunya virus is a mosquito-borne arthrogenic alphavirus that has recently reemerged to produce the largest epidemic ever documented for this virus. Here we describe a new adult wild-type mouse model of chikungunya virus arthritis, which recapitulates the self-limiting arthritis, tenosynovitis, - myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, - NK cells - the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), - gamma interferon (IFN-gamma). Infection with a virus isolate from the recent Reunion Isl- epidemic induced significantly more mononuclear infiltrates, proinflammatory mediators, - foot swelling than did an Asian isolate from the 1960s. Primary mouse macrophages were shown to be productively infected with chikungunya virus; however, the depletion of macrophages ameliorated rheumatic disease - prolonged the viremia. Only 1 microg of an unadjuvanted, inactivated, whole-virus vaccine derived from the Asian isolate completely protected against viremia - arthritis induced by the Reunion Isl- isolate, illustrating that protection is not strain specific - that low levels of immunity are sufficient to mediate protection. IFN-alpha treatment was able to prevent arthritis only if given before infection, suggesting that IFN-alpha is not a viable therapy. Prior infection with Ross River virus, a related arthrogenic alphavirus, - anti-Ross River virus antibodies protected mice against chikungunya virus disease, suggesting that individuals previously exposed to Ross River virus should be protected from chikungunya virus disease. This new mouse model of chikungunya virus disease thus provides insights into pathogenesis - a simple - convenient system to test potential new interventions.
Imprenta: Journal of Virology, v. 84, n. 16, p. 8021-8032, 2010
Identificador do objeto digital: 10.1128/JVI.02603-09
Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2010
