[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Animal model of arthritis and myositis induced by the Mayaro virus
Franciele Martins Santos, Roberto Sousa Dias, Michelle Dias de Oliveira, Isabella Cristina Toledo Alves Costa, Luciana de Souza Fernandes, Carine Ribeiro Pessoa, Sérgio Luis Pinto da Matta, Vivian Vasconcelos Costa, Danielle G. Souza, Cynthia Canêdo da Silva, Sérgio Oliveira de Paula
Published: May 3, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007375 / This is an uncorrected proof.
The Mayaro virus (MAYV) is an endemic arbovirus in South American countries, where it is responsible for sporadic outbreaks of Mayaro fever. Clinical manifestations include fever, headache, ocular pain, rash, myalgia, and debilitating and persistent polyarthralgia. Understanding the mechanisms associated with MAYV-induced arthritis is of great importance due to the potential for its emergence, urbanization and dispersion to other regions.
15-day old Balb/c mice were infected by two distinct pathways, below the forelimb and in the rear footpad. Animals were observed for a period of 21 days. During this time, they were monitored every 24 hours for disease signs, such as weight loss and muscle weakness. Histological damage in the muscles and joints was evaluated 3, 7, 10, 15 and 20 days post-infection. The cytokine profile in serum and muscles during MAYV infection was evaluated by flow cytometry at different post-infection times. For pain analysis, the animals were submitted to the von Frey test and titre in different organs was evaluated throughout the study to obtain viral kinetics.
Infection by two distinct pathways, below the forelimb and in the rear footpad, resulted in a homogeneous viral spread and the development of acute disease in animals. Clinical signs were observed such as ruffled fur, hunched posture, eye irritation and slight gait alteration. In the physical test, both groups presented loss of resistance, which was associated with histopathological damage, including myositis, arthritis, tenosynovitis and periostitis. The immune response was characterized by a strong inflammatory response mediated by the cytokines TNF-α, IL-6 and INF-γ and chemokine MCP-1, followed by the action of IL-10 and IL-4 cytokines.
The results showed that Balb/c mice represent a promising model to study mechanisms involved in MAYV pathogenesis and for future antiviral testing.
The Mayaro virus, although restricted to some regions of Latin America, has great potential for emergence, which makes it of great medical-scientific interest. Therefore, pathogenesis study of the MAYV in an animal model has fundamental importance for the determination of viral and host factors that contribute to disease development. In addition, it will allow develop and evaluate the effectiveness of possible antiviral agents. In this study, the authors were able to standardize a disease model for the MAYV in BALB / c mice. From the obtained data it is possible to observe the induction of acute arthritis and myositis, accompanied by the reduction of physical strength of the animals. As described for other alphaviruses in both animal and patient models, the proinflammatory mediators TNF-α, IL-6, INF-γ and MCP-1 were elevated in the serum of MAYV-infected animals and therefore appeared to be mediators which also play an important role in the pathogenesis of MAYV.
Citation: Santos FM, Dias RS, de Oliveira MD, Costa ICTA, Fernandes LdS, Pessoa CR, et al. (2019) Animal model of arthritis and myositis induced by the Mayaro virus. PLoS Negl Trop Dis 13(5): e0007375. https://doi.org/10.1371/journal.pntd.0007375
Editor: William Klimstra, University of PittsburghUniversity of PittsburghUniversity of PittsburghUniversity of Pittsburgh, UNITED STATES
Received: September 4, 2018; Accepted: April 9, 2019; Published: May 3, 2019
Copyright: © 2019 Santos et al. 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 credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The authors are grateful for the financial support of CAPES, CNPq and FAPEMIG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Keywords: Mayaro virus; Viral pathogenesis; Animal models.