A Mouse Model for Studying Post-Acute Arthritis of Chikungunya.

Aileen Y Chang,Abigail J Porzucek,Arnold M Schwartz,Gary L Simon,Christopher N Mores,St Patrick Reid,Sarah R Tritsch,Margaux Seyler-Schmidt,Patricia S Latham,Arielle Glass

doi:10.3390/microorganisms9091998

Aileen Y Chang, Abigail J Porzucek + Show 8 more

Open Access

https://doi.org/10.3390/microorganisms9091998

Copy DOI

Abstract

Chikungunya virus (CHIKV) was introduced to the Americas in 2013, causing two million infections across over thirty countries. CHIKV causes a chronic debilitating arthritis in one fourth of infected individuals and currently evidence-based targeted therapies for the treatment of CHIKV arthritis are lacking. Multiple mouse models of chikungunya have been developed to study acute CHIKV infection. In humans, post-CHIKV arthritis may persist for months to years after viremia from a CHIKV infection has resolved. Therefore, the development of a mouse model of post-acute arthritis of chikungunya may facilitate the study of potential novel therapeutics for this arthritis. In this article we describe the development of a wild-type immunocompetent C57BL/6 mouse model for post-acute arthritis of chikungunya, including a histologic inflammation scoring system, as well as suggestions for how this mouse model may be used to examine the efficacy of novel therapies for CHIKV arthritis.

Highlights

Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that was introduced to the Americas in 2013, causing two million infections across over thirty countries [1]
16–21 DPI, wherein the mice are no longer viremic but still display prominent histologic evidence of inflammation, that would be the ideal window for studies of investigational drugs; (3) the composite histologic inflammation score may be of utility for determining efficacy outcomes; and (4) tarsal joint swelling is only present for a limited duration during viremia, which excludes tarsal joint swelling as a valuable endpoint for post-acute arthritis of chikungunya drug studies
We found that tarsal joint swelling was only significant for a duration of approximately 10 days during viremia, which may preclude the use of tarsal joint swelling as a valuable endpoint for post-CHIKV arthritis drug studies

Summary

Introduction

Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that was introduced to the Americas in 2013, causing two million infections across over thirty countries [1]. It affects an estimated 1 million people annually [2] and causes persistent arthritis in one fourth of patients that may last for months to years [3] that is responsible for significant morbidity [4] and loss of economic productivity [5]. The arthritic potential of CHIKV is not unique; other alphaviruses such as Mayaro, Sinbis, Ross River, and O’nyong’nyong cause severe arthritis [6]. Investigation of the targeted therapies for post-acute arthritis of chikungunya is needed

Methods

Results

Conclusion