Chikungunya Virus Arthritis in Adult Wild-Type Mice
Joy Gardner,Itaru Anraku,Thuy T. Le,Thibaut Larcher,Lee Major,Pierre Roques,Wayne A. Schroder,Stephen Higgs,Andreas Suhrbier,Andreas Suhrbier +9 more
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TLDR
A new adult wild-type mouse model of chikungunya virus arthritis is described, which recapitulates the self-limiting arthritis, tenosynovitis, and myositis seen in humans and provides insights into pathogenesis and a simple and convenient system to test potential new interventions.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-α), and gamma interferon (IFN-γ). 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 μg 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-α treatment was able to prevent arthritis only if given before infection, suggesting that IFN-α 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.read more
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Journal ArticleDOI
Chikungunya: a re-emerging virus
Felicity J. Burt,Micheal S Rolph,Nestor E. Rulli,Nestor E. Rulli,Suresh Mahalingam,Mark T. Heise +5 more
TL;DR: This Seminar focuses on the re-emergence of chikungunya, the clinical manifestations, pathogenesis of virus-induced arthralgia, diagnostic techniques, and various treatment modalities.
Journal ArticleDOI
Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy.
Simon Djamel Thiberville,Nanikaly Moyen,Laurence Dupuis-Maguiraga,Antoine Nougairède,Ernest A. Gould,Pierre Roques,Xavier de Lamballerie +6 more
TL;DR: A comprehensive review of chikungunya fever and CHIKV, including clinical data, epidemiological reports, therapeutic aspects and data relating to animal models for in vivo laboratory studies, including Supplementary Tables of all WHO outbreak bulletins, ProMED Mail alerts, viral sequences available on GenBank, and PubMed reports of clinical cases and seroprevalence studies are provided.
Journal ArticleDOI
Arthritogenic alphaviruses—an overview
TL;DR: Mosquito-transmitted alphaviruses causing human rheumatic disease are globally distributed and include chikungunya virus, Ross River virus, Barmah Forest virus, Sindbis virus, o'nyong-nyong virus and Mayaro virus.
Journal ArticleDOI
Chikungunya Virus-associated Long-term Arthralgia: A 36-month Prospective Longitudinal Study
Clémentine Schilte,Clémentine Schilte,Frédérik Staikovsky,Thérèse Couderc,Thérèse Couderc,Yoann Madec,Florence Carpentier,Florence Carpentier,Somar Kassab,Matthew L. Albert,Matthew L. Albert,Matthew L. Albert,Marc Lecuit,Alain Michault +13 more
TL;DR: It is demonstrated that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.
Journal ArticleDOI
Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus
Pankaj Pal,Kimberly A. Dowd,James D. Brien,Melissa A. Edeling,Sergey Gorlatov,Syd Johnson,Iris Lee,Wataru Akahata,Gary J. Nabel,Mareike K. S. Richter,Jolanda M. Smit,Daved H. Fremont,Theodore C. Pierson,Mark T. Heise,Michael S. Diamond +14 more
TL;DR: Administration of a single dose of a combination of two neutralizing MAbs limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death.
References
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Journal ArticleDOI
Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus.
Marie Vazeille,Sara Moutailler,D. Coudrier,Claudine Rousseaux,Huot Khun,Michel Huerre,Julien Thiria,Jean-Sébastien Dehecq,Didier Fontenille,Isabelle Schuffenecker,Philippe Desprès,Anna-Bella Failloux +11 more
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Journal ArticleDOI
A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease.
Thérèse Couderc,Fabrice Chrétien,Clémentine Schilte,Olivier Disson,Madly Brigitte,Florence Guivel-Benhassine,Yasmina Touret,G. Barau,Nadège Cayet,Isabelle Schuffenecker,Philippe Desprès,Fernando Arenzana-Seisdedos,Alain Michault,Matthew L. Albert,Marc Lecuit +14 more
TL;DR: It is shown that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent, and the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHikV-associated disease are identified.
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