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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-\u03b1), and gamma interferon (IFN-\u03b3). 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 \u03bcg 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-\u03b1 treatment was able to prevent arthritis only if given before infection, suggesting that IFN-\u03b1 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.<\/jats:p>","DOI":"10.1128\/jvi.02603-09","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T22:37:56Z","timestamp":1275518276000},"page":"8021-8032","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":427,"title":["Chikungunya Virus Arthritis in Adult Wild-Type Mice"],"prefix":"10.1128","volume":"84","author":[{"given":"Joy","family":"Gardner","sequence":"first","affiliation":[{"name":"Queensland Institute of Medical Research, Australian Centre for International and Tropical Health, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Anraku","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Australian Centre for International and Tropical Health, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy T.","family":"Le","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Australian Centre for International and Tropical Health, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Larcher","sequence":"additional","affiliation":[{"name":"Institut National de Recherche Agronomique, Unite\u0301 Mixte de Recherche 703, Ecole Nationale Ve\u0301te\u0301rinaire, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Major","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Australian Centre for International and Tropical Health, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Roques","sequence":"additional","affiliation":[{"name":"CEA, Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne A.","family":"Schroder","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Australian Centre for International and Tropical Health, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Higgs","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Suhrbier","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Australian Centre for International and Tropical Health, Brisbane, Australia"},{"name":"Griffith Medical Research College, Griffith University, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00051-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2105"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535342"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.04.001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.11.1799"},{"key":"e_1_3_2_7_2","first-page":"313","volume":"63","year":"1983","unstructured":"Brighton, S. 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