Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response

Abstract

Mayaro virus (MAYV), an alphavirus similar to chikungunya virus (CHIKV), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen.

In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease

“…Chronic joint inflammation and pain are the hallmarks of disease in patients with alphavirus infections 27,45 . Pain is one of the classical signs of the inflammatory process in which sensitization of the nociceptors is the common denominator 46 .…”

“…Long-term arthralgia after MAYV infection is associated with sustained pro-inflammatory cytokine responses 27 . We evaluated the production of inflammatory mediators during the course of MAYV infection in BALB/c mice.…”

“…MAYV causes an acute debilitating disease that is associated with long-term arthralgia and persistent pain in more than 50% of the affected individuals 27 . There is no specific treatment or available vaccine to treat MAYV infection.…”

Deciphering the Nucleotide and RNA Binding Selectivity of the Mayaro Virus Macro Domain

“…Despite its endemic distribution in South America, the induced disease has a clinical picture similar to the Old World Alphaviruses [6]. In particular, symptoms include mild-to-severe Dengue-like febrile syndrome, characterized by fever, headache, rash, myalgia, arthralgia and arthritis, which can be debilitating and can persist for months [4,7,8]. These clinical manifestations are reported also in the Chikungunya virus (CHIKV) disease.…”

Mayaro fever in an HIV-infected patient suspected of having Chikungunya fever

“…MAYV causes a mild to severe illness characterized by fever, headache, rash, malaise, myalgia, large joint arthralgia and, sometimes, arthritis, similar to that caused by CHIKV. Although MAYV does not cause hemorrhagic fever, it can be very debilitating due to the arthritis that can persist for months (2) . Since the first description of autochthonous cases of Chikungunya fever in the Americas in November 2013 (3) , Brazil's Ministry of Health compiled a national contingency plan, aiming to establish appropriate strategies to prevent the import and spread of the virus and to guide clinical management of the disease (4) .…”