microorganisms Article A Mouse Model for Studying Post-Acute Arthritis of Chikungunya Aileen Y. Chang 1, * , Sarah R. Tritsch 2 , Abigail J. Porzucek 2 , Arnold M. Schwartz 3 , Margaux Seyler-Schmidt 2 , Arielle Glass 2 , Patricia S. Latham 3 , St. Patrick Reid 4 , Gary L. Simon 1 and Christopher N. Mores 2   Citation: Chang, A.Y.; Tritsch, S.R.; Porzucek, A.J.; Schwartz, A.M.; Seyler-Schmidt, M.; Glass, A.; Latham, P.S.; Reid, S.P.; Simon, G.L.; Mores, C.N. A Mouse Model for Studying Post-Acute Arthritis of Chikungunya. Microorganisms 2021, 9, 1998. https://doi.org/10.3390/ microorganisms9091998 Academic Editors: Kevin K. Arien, Koen Bartholomeeusen and Miguel A. Martín-Acebes Received: 1 July 2021 Accepted: 14 September 2021 Published: 21 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Medicine, School of Medicine and Health Sciences, George Washington University, 2150 Pennsylvania Ave 5-416, Washington, DC 20037, USA; gsimon@mfa.gwu.edu 2 Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA; sarahtritsch@email.gwu.edu (S.R.T.); abbporz@gmail.com (A.J.P.); mdeja17@gwmail.gwu.edu (M.S.-S.); arielleglass@email.gwu.edu (A.G.); cmores@email.gwu.edu (C.N.M.) 3 Department of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA; arnies@gwu.edu (A.M.S.); pslath@gwu.edu (P.S.L.) 4 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68182, USA; patrick.reid@unmc.edu * Correspondence: chang@email.gwu.edu 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. Keywords: chikungunya; mouse model; arthritis; arthritis therapy; myositis; bone erosion; synovitis 1. Introduction Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that was intro- duced 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 also cause severe arthritis [6]. There is currently no standard evidence-based treatment for alphavirus-induced arthritis. Investigation of the targeted therapies for post-acute arthritis of chikungunya is needed. Mouse models of CHIKV infection provide valuable information on the pathogenesis of arthritis [7–10] and its response to various therapies [11–13]. Mouse models demonstrate infiltration of monocytes [8,10], macrophages [8,10], and lymphocytes [9,10] in inflamed joints with significant effects on resident fibroblasts [7,14]. Mice infected with CHIKV demonstrate foot swelling and histologic evidence of acute and persistent arthritis [8–10]. Specifically, subcutaneous footpad inoculation of adult wild-type immunocompetent C57BL/6 mice with pathogenic strains of CHIKV results in acute foot swelling, myositis, tenosynovitis, and arthritis [8–13]. In this model, while the swelling usually resolves within the first 2 weeks of infection [8,9], chronic disease can be observed histologically for at least Microorganisms 2021, 9, 1998. https://doi.org/10.3390/microorganisms9091998 https://www.mdpi.com/journal/microorganisms