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  • Chikungunya Virus Arthritis in Adult Wild-Type Mice

    Author(s)
    Gardner, J
    Anraku, I
    Le, TT
    Larcher, T
    Major, L
    Roques, P
    Schroder, WA
    Higgs, S
    Suhrbier, A
    Griffith University Author(s)
    Schroder, Wayne
    Suhrbier, Andreas
    Year published
    2010
    Metadata
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    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 a new adult wild-type mouse model of chikungunya virus arthritis, which recapitulates the self-limiting arthritis, tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, and NK cells and the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-{alpha}), and gamma interferon (IFN-{gamma}). Infection with a virus isolate from the recent Reunion ...
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    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, and myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, and NK cells and the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-{alpha}), and gamma interferon (IFN-{gamma}). Infection with a virus isolate from the recent Reunion Island epidemic induced significantly more mononuclear infiltrates, proinflammatory mediators, and 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 and prolonged the viremia. Only 1 姠of an unadjuvanted, inactivated, whole-virus vaccine derived from the Asian isolate completely protected against viremia and arthritis induced by the Reunion Island isolate, illustrating that protection is not strain specific and 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, and 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 and a simple and convenient system to test potential new interventions.
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    Journal Title
    Journal of Virology
    Volume
    84
    Issue
    16
    DOI
    https://doi.org/10.1128/JVI.02603-09
    Subject
    Microbiology not elsewhere classified
    Biological Sciences
    Agricultural and Veterinary Sciences
    Medical and Health Sciences
    Publication URI
    http://hdl.handle.net/10072/35731
    Collection
    • Journal articles

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