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Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation of<jats:italic>Rag1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type and<jats:italic>Rag1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans.<\/jats:p>","DOI":"10.1128\/jvi.02666-13","type":"journal-article","created":{"date-parts":[[2013,10,17]],"date-time":"2013-10-17T04:36:32Z","timestamp":1381984592000},"page":"13878-13888","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":244,"title":["Chronic Joint Disease Caused by Persistent Chikungunya Virus Infection Is Controlled by the Adaptive Immune Response"],"prefix":"10.1128","volume":"87","author":[{"given":"David W.","family":"Hawman","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"Graduate Program in Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina A.","family":"Stoermer","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"Graduate Program in Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Pal","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Oko","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"Department of Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.64"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60281-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001446"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400044442"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82858-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01603-09"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.07.004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61779-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1705.101873"},{"key":"e_1_3_2_11_2","unstructured":"OlivaOSan MartinJLNasciRS. 2011. 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