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Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory
Mariana G Cavalheiro1, Leandro Silva DA Costa1, Holmes S Campos1
1Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco E, Sala 18, 21941-902 Rio de Janeiro, RJ Brasil.
Abstract:
Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection.
Insights
Mayaro virus (MAYV) infects macrophages, causing cell death and triggering inflammation through reactive oxygen species (ROS) and TNF. This study reveals key mechanisms in MAYV-induced arthritis pathogenesis.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Alphaviruses cause global public health issues, with Old World types inducing arthritis and New World types causing encephalitis.
- Mayaro virus (MAYV), found in South America, is phylogenetically linked to Old World alphaviruses but causes arthralgia, presenting a unique case.
- The molecular and cellular basis of MAYV-induced arthritis remains poorly understood.
Purpose of the Study:
- To investigate the cellular targets of Mayaro virus (MAYV) infection.
- To elucidate the molecular mechanisms underlying MAYV-induced arthritis pathogenesis.
- To explore the role of macrophages and inflammatory mediators in MAYV infection.
Main Methods:
- Investigated macrophage susceptibility to MAYV infection.
- Assessed MAYV-induced apoptosis in macrophages.
- Measured TNF cytokine expression following MAYV infection.
- Quantified reactive oxygen species (ROS) production during MAYV infection.
- Evaluated the effect of antioxidant treatment on TNF secretion.
Main Results:
- Macrophages were identified as target cells for MAYV, leading to apoptosis.
- MAYV replication induced TNF expression in macrophages, contributing to an inflammatory profile.
- Increased ROS production was observed early in infection, preceding TNF secretion.
- Antioxidant treatment post-infection significantly inhibited TNF secretion, implicating ROS in MAYV-induced inflammation.
Conclusions:
- Macrophages are crucial cellular players in Mayaro virus pathogenesis.
- Reactive oxygen species (ROS) play a significant role in mediating inflammation during MAYV infection.
- Understanding MAYV's interaction with macrophages and ROS provides insights into arthritis development and potential therapeutic targets.
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