title: A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.
abstract: Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Seymour
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: A Paige
authors.initials: AP
authors.lastname: Adams
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Grace
authors.initials: G
authors.lastname: Leal
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Maria D H
authors.initials: MD
authors.lastname: Alcorn
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D018771:Arthralgia / Q000503:physiopathology*; D001483:Base Sequence; D065632:Chikungunya Fever / Q000276:immunology* / Q000503:physiopathology*; D002646:Chikungunya virus / Q000235:genetics*; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017423:Sequence Analysis, RNA; D019562:Viral Load; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; D014765:Viral Vaccines; C064658:RAG-1 protein