Mayaro Virus Induction of Oxidative Stress is Associated With Liver Pathology in a Non-Lethal Mouse Model

Camila Carla Da Silva Caetano,Ariane Coelho Ferraz,Thalles De Freitas Castro,Silvana De Queiroz Silva,Fernanda Caetano Camini,Cintia Lopes De Brito Magalhães,José Carlos De Magalhães,Rafaela Lameira Souza Lima,Letícia Trindade Almeida,Tales Fernando Da Silva,Cláudia Martins Carneiro,Mayara Medeiros De Freitas Carvalho,Breno De Mello Silva

doi:10.1038/s41598-019-51713-9

Camila Carla Da Silva Caetano, Ariane Coelho Ferraz + Show 11 more

Open Access

https://doi.org/10.1038/s41598-019-51713-9

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Abstract

Mayaro virus (MAYV) causes Mayaro fever in humans, a self-limiting acute disease, with persistent arthralgia and arthritis. Although MAYV has a remerging potential, its pathogenic mechanisms remain unclear. Here, we characterized a model of MAYV infection in 3–4-week BALB/c mice. We investigated whether the liver acts as a site of viral replication and if the infection could cause histopathological alterations and an imbalance in redox homeostasis, culminating with oxidative stress. MAYV-infected mice revealed lower weight gain; however, the disease was self-resolving. High virus titre, neutralizing antibodies, and increased levels of aspartate and alanine aminotransferases were detected in the serum. Infectious viral particles were recovered in the liver of infected animals and the histological examination of liver tissues revealed significant increase in the inflammatory infiltrate. MAYV induced significant oxidative stress in the liver of infected animals, as well as a deregulation of enzymatic antioxidant components. Collectively, this is the first study to report that oxidative stress occurs in MAYV infection in vivo, and that it may be crucial in virus pathogenesis. Future studies are warranted to address the alternative therapeutic strategies for Mayaro fever, such as those based on antioxidant compounds.

Highlights

Mayaro virus (MAYV) is an arbovirus member of the Alphavirus genus and Togaviridae family
In terms of host mechanisms that address disease pathology, several studies have reported that the oxidative stress induced by virus can affect several aspects for the disease, demonstrating that inflammatory process and the stress response are important factors in the viral pathogenesis, thereby contributing to the severity of the disease[23,26,35,36,37,38,39,40]
To better characterize MAYV pathogenesis, we evaluated the markers of oxidative injury and antioxidants components in liver of BALB/c mice after MAYV infection

Summary

Introduction

Mayaro virus (MAYV) is an arbovirus member of the Alphavirus genus and Togaviridae family. A majority of MAYV infections in humans occur in people who visit the forests frequently; in the past few years, these infections have been reported in urban/periurban areas, indicating the potential urbanization of Mayaro fever in Brazil[13,14,15,16]. Despite the outbreaks and spread of Mayaro fever into new locations, few studies are available on the cellular and molecular mechanisms of the disease and its pathogenesis. Reactive oxygen species (ROS) are reactive atoms or molecules generated by physiological or pathological processes[28]. Their abundance can cause cellular damage leading to the loss of integrity and functionality[29]

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