Chikungunya Virus Arthritis in Adult Wild-Type Mice

• DOI: 10.1128/jvi.02603-09
• Publication Date: 2010-06-03T02:37:56Z
• Authors: Joy Gardner; Itaru Anraku; Thuy T. Le; Thibaut Larcher; Lee Major; Pierre Roques; Wayne A. Schroder; Stephen Higgs; Andreas Suhrbier
• Keywords: Alphavirus infection

ABSTRACT 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 new adult wild-type mouse model of chikungunya arthritis, which recapitulates self-limiting tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with prolific infiltrate monocytes, macrophages, NK cells production monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ). Infection isolate from recent Reunion Island induced significantly more mononuclear infiltrates, proinflammatory mediators, foot swelling than did an Asian 1960s. Primary macrophages were shown be productively infected virus; however, depletion ameliorated rheumatic prolonged viremia. Only μg unadjuvanted, inactivated, whole-virus vaccine derived completely protected against viremia arthritis by isolate, illustrating protection not strain specific low levels immunity are sufficient mediate protection. IFN-α treatment able prevent only if given before infection, suggesting viable therapy. Prior infection Ross River virus, related alphavirus, anti-Ross antibodies mice disease, individuals previously exposed should disease. This thus provides insights into pathogenesis simple convenient system test potential interventions.