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.
Highlights
Viral arthritides are usually acute diseases that in some cases may progress to incapacitating and long lasting arthropathies
The studies are almost completely restricted to clinical data, which show that, to what is observed in the infection with Old World alphaviruses, Mayaro virus (MAYV)-infected patients presented a high prevalence of arthralgia (Azevedo et al 2009, Mourão et al 2012, Pinheiro et al 1981), diffuse myalgia (Vieira et al 2015, Theilacker et al 2013), highly painful swelling of small finger joints (Friedrich-Jänicke et al 2014) and polyarthralgia of the hands, wrists, elbows and ankles (Slegers et al 2014)
We demonstrated for the first time that macrophages, cells with an important role in arthritis development, are target cells for MAYV
Summary
Viral arthritides are usually acute diseases that in some cases may progress to incapacitating and long lasting arthropathies. A recent example is the Chikungunya virus (CHIKV) epidemics in Americas. This virus was responsible for outbreaks in Africa and Asia, but reached Caribbean countries in 2013 (Mowatt and Jackson 2014). In the end of 2014, the first cases were reported in Brazil One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and clusters in phylogenetic analyses with the Old World alphaviruses (Lavergne et al 2006)
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