Abstract
Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3–/–, Aim2–/–, Asc–/–and Casp1/11–/–mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1β. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1β and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans.
Highlights
Arboviruses are one of the public health authorities major concerns, contributing to an increasing awareness of emerging infections worldwide
Viruses transmitted by mosquitoes have recently received huge attention from the media because the epidemics caused by Zika and chikungunya virus rapidly spread to new areas and infected a large number of individuals
It causes a highly inflammatory disease, called Mayaro fever, and acute disease is often followed by a prolonged arthralgia mediated by chronic inflammation that can last months or years
Summary
Arboviruses are one of the public health authorities major concerns, contributing to an increasing awareness of emerging infections worldwide. After the spread of chikungunya virus (CHIKV) to new areas of the globe and the emergence of Zika virus (ZIKV), surveillance systems worldwide are focusing much attention on tracking the arboviral epidemic [1]. Haemagogus mosquitoes have been documented as the main vectors of MAYV, and Aedes aegypti has been found to be a competent vector, a feature that has alerted authorities to the eminent possibility that MAYV emerge as a global pathogen [1,9]. MAYV is the causative agent of Mayaro fever, a neglected endemic infection that is characterized by nonspecific symptoms such as high fever, rash, arthralgia, myalgia and headache. Similar to CHIKV infection, MAYV is associated with a prolonged arthralgia which can last for months or even years, possibly due to chronic inflammation [10,11]. The mechanisms underlying these clinical signs are still not elucidated
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