Immunopathological mechanisms and targeted intervention strategies for chronic chikungunya arthritis: from viral...

Chronic chikungunya arthritis (CCA) is a major long-term sequela of Chikungunya virus (CHIKV) infection. Its pathogenesis involves persistent viral reservoirs in joint tissues, metabolic reprogramming of myeloid cells, dysregulated Treg/Th17 immunity, and autoimmune-like tissue injury. This review integrates recent advances in virology, immunometabolism, and clinical pathology to propose a four-stage pathological cascade: "viral persistence", "myeloid metabolic dysregulation", "Treg/Th17 imbalance", and "autoimmunity-like injury". Key cytokine networks and molecular interactions at each stage are summarized. Based on this model, we outline stage-specific therapeutic strategies, including antiviral agents targeting Mxra8 or nsP1 (Stage I), metabolic modulators such as HIF-1α inhibitors and IL-1β blockade (Stage II), immune-restorative therapies such as low-dose IL-2 and CTLA-4-Ig (Stage III), and anti-inflammatory biologics or DMARDs for RA-like pathology (Stage IV). This framework provides a mechanistic basis for precision intervention and supports the development of biomarkers and clinical trial designs for CCA.