Biochemical Mechanisms of Extracellular Matrix Degradation in Chikungunya Infection

Chronic arthritis caused by the Chikungunya virus (CHIKV) represents a serious global health problem, with a significant proportion of patients developing debilitating and persistent arthropathy. This review critically analyzes the biochemical mechanisms underlying the irreversible destruction of the joint extracellular matrix (ECM), going beyond the acute viral inflammatory response. The objective is to describe the current evidence on the biochemical mechanisms, with an emphasis on the MMP/TIMP imbalance, that lead to ECM degradation in chronic CHIKV arthropathy. The main findings highlight that CHIKV, thanks to its tropism for chondrocytes mediated by receptors such as Mxra8 and CD147, triggers a “proteolytic storm.” This involves sustained overexpression of MMPs (especially MMP-1, -9, -13) and a paradoxical imbalance of TIMPs, where elevated levels of TIMP-2 are associated with chronicity. Degradation follows an orderly sequence: initial loss of agrecan by ADAMTS, followed by irreversible lysis of type II collagen. Finally, chondrocyte apoptosis (via IGFBP-3) and the generation of matrikines (such as the 32-mer fragment of aggrecan) that activate nociceptors via TLR2 explain chondropenia and chronic pain. It is concluded that CHIKV arthropathy is essentially a disease of the ECM, where biochemical degradation and pain signaling are mutually perpetuated.