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Mayaro Virus Induction of Oxidative Stress is Associated With Liver Pathology in a Non-Lethal Mouse Model
Camila Carla da Silva Caetano1, Fernanda Caetano Camini1, Letícia Trindade Almeida1
1Postgraduate Program of Biological Science, Biological Sciences Research Center, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
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.
Insights
Mayaro virus (MAYV) infection in mice causes self-resolving disease and liver inflammation. This study reveals MAYV induces oxidative stress in the liver, a key factor in its pathogenesis.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Mayaro virus (MAYV) causes Mayaro fever, a disease with potential for re-emergence.
- The pathogenic mechanisms of MAYV, particularly in vivo, are not fully understood.
- Investigating MAYV pathogenesis in a relevant animal model is crucial.
Purpose of the Study:
- To establish and characterize a mouse model for MAYV infection.
- To investigate the liver as a site of viral replication and its pathological consequences.
- To determine if MAYV infection induces oxidative stress and alters redox homeostasis in the liver.
Main Methods:
- Establishment of a MAYV infection model in BALB/c mice.
- Monitoring of clinical signs, weight gain, and viral load.
- Assessment of liver histopathology, serum liver enzymes (AST, ALT), and antibody responses.
- Evaluation of oxidative stress markers and antioxidant enzyme activity in liver tissues.
Main Results:
- MAYV-infected mice exhibited reduced weight gain but self-resolving disease.
- High viral titers, neutralizing antibodies, and elevated AST/ALT levels were observed.
- Infectious viral particles were detected in the liver, with significant inflammatory infiltrates.
- MAYV infection induced significant oxidative stress and altered antioxidant enzyme levels in the liver.
Conclusions:
- This study demonstrates that Mayaro virus infection in mice leads to liver inflammation and oxidative stress.
- Oxidative stress appears to play a critical role in the in vivo pathogenesis of MAYV.
- Findings suggest that antioxidant compounds may represent a potential therapeutic strategy for Mayaro fever.
