A rodent model of chikungunya virus infection in RAG1 <sup>-/-</sup> mice, with features of persistence, for vaccine safety evaluation

Robert Seymour, A. Paige Adams, Grace Leal, Maria D H Alcorn, Scott Weaver

Research output: Contribution to journalArticle

12 Citations (Scopus)

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<sup>-/-</sup>) 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.

Original languageEnglish (US)
Article numbere0003800
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number6
DOIs
StatePublished - Jun 26 2015

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Chikungunya virus
Rodentia
Vaccines
Safety
Arthralgia
RAG-1 Genes
Alphavirus
Attenuated Vaccines
Gene Knockout Techniques
Aptitude
RNA Viruses
Adaptive Immunity
Neurologic Manifestations
Exanthema
Knockout Mice
Arthritis
Disease Outbreaks
Chikungunya Fever
B-Lymphocytes
Fever

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

A rodent model of chikungunya virus infection in RAG1 <sup>-/-</sup> mice, with features of persistence, for vaccine safety evaluation. / Seymour, Robert; Adams, A. Paige; Leal, Grace; Alcorn, Maria D H; Weaver, Scott.

In: PLoS Neglected Tropical Diseases, Vol. 9, No. 6, e0003800, 26.06.2015.

Research output: Contribution to journalArticle

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