Immunopathogenesis of Mayaro Virus-Induced Chronic Arthritis: From Inflammatory Pathways to Targeted Therapeutic Strategies.

Abstract

Background: Mayaro virus (MAYV), an emerging and endemic arthritogenic alphavirus in tropical regions of South America, represents a growing public health threat and is primarily transmitted by Haemagogus genus mosquitoes. Although MAYV infection typically results in a self-limiting febrile illness, a significant proportion of patients develop chronic musculoskeletal symptoms, notably persistent arthralgia and arthritis.

Rationale: This comprehensive review examines the immunopathogenesis of MAYV infection, focusing on the complex dynamics of innate and adaptive immune responses and the mechanisms contributing to postviral joint inflammation. Particular emphasis is placed on macrophage activation, inflammasome signaling (notably NLRP3), and the intrinsic susceptibility of joint-resident cells, including synoviocytes, chondrocytes, and osteoblasts. Furthermore, this review discusses recent evidence of viral persistence within tissue reservoirs as a key driver of chronic pathology and proposes a conceptual model in which MAYV persistence within joint-resident cells sustains chronic NLRP3 inflammasome activation, thereby driving long-term arthralgia. Additionally, the viral strategies for immune evasion-chiefly mediated by the nonstructural protein nsP2-are discussed in the context of interferon suppression and transcriptional shut-off.

Conclusion: The article provides a critical evaluation of current and developing therapeutic strategies, including antiviral agents such as favipiravir and immunomodulatory agents targeting IL-1β, tumor necrosis factor, and IL-6 signaling. Understanding the interplay between viral determinants and host immune responses is critical for the rational design of effective interventions against MAYV-induced chronic inflammation and arthritis.