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A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation

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 de...

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Autores principales: Seymour, Robert L., Adams, A. Paige, Leal, Grace, Alcorn, Maria D. H., Weaver, Scott C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482609/
https://www.ncbi.nlm.nih.gov/pubmed/26115459
http://dx.doi.org/10.1371/journal.pntd.0003800
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author Seymour, Robert L.
Adams, A. Paige
Leal, Grace
Alcorn, Maria D. H.
Weaver, Scott C.
author_facet Seymour, Robert L.
Adams, A. Paige
Leal, Grace
Alcorn, Maria D. H.
Weaver, Scott C.
author_sort Seymour, Robert L.
collection PubMed
description 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.
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spelling pubmed-44826092015-06-29 A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation Seymour, Robert L. Adams, A. Paige Leal, Grace Alcorn, Maria D. H. Weaver, Scott C. PLoS Negl Trop Dis Research Article 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. Public Library of Science 2015-06-26 /pmc/articles/PMC4482609/ /pubmed/26115459 http://dx.doi.org/10.1371/journal.pntd.0003800 Text en © 2015 Seymour et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Seymour, Robert L.
Adams, A. Paige
Leal, Grace
Alcorn, Maria D. H.
Weaver, Scott C.
A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation
title A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation
title_full A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation
title_fullStr A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation
title_full_unstemmed A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation
title_short A Rodent Model of Chikungunya Virus Infection in RAG1 (-/-) Mice, with Features of Persistence, for Vaccine Safety Evaluation
title_sort rodent model of chikungunya virus infection in rag1 (-/-) mice, with features of persistence, for vaccine safety evaluation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482609/
https://www.ncbi.nlm.nih.gov/pubmed/26115459
http://dx.doi.org/10.1371/journal.pntd.0003800
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