Tactical Paralysis: The Interplay Between Chikungunya Virus and Host Mitochondrial Dynamics in Immune Evasion and Metabolic Remodeling

Chikungunya virus (CHIKV) is an expanding alphavirus causing acute febrile illness, yet its most debilitating signature remains the refractory chronic arthralgia persisting for months or years. While traditional paradigms focused on viral-mediated host shutoff, emerging evidence points to a more insidious orchestrated sabotage within the joint niche. This review deconstructs the tactical paralysis of host mitochondrial dynamics driven by CHIKV. We delineate how specific viral components (nsP2, TF, and 6K) act as molecular wedges or post-translational modifiers that hijack host fission/fusion machinery (Drp1/Mfn2), driving the mitochondrial network into compulsive fragmentation. Crucially, this morphological collapse operates as a double-edged sword: in the acute phase, it disrupts the MAVS signalosome to mute the type I interferon response; in the chronic phase, it cascades into a profound immunometabolic rewiring within the synovial microenvironment. In synovial macrophages, mitochondrial fragmentation ruptures the tricarboxylic acid (TCA) cycle, causing succinate accumulation that epigenetically locks cells into a persistent, pro-inflammatory M1 phenotype, establishing a destructive "metabolic memory." Concurrently, in fibroblast-like synoviocytes (FLS), retrograde signaling from mitochondrial ROS and cytosolic mtDNA leakage prompts a pseudo-malignant transformation, accelerating extracellular matrix degradation via MMP-13 and RANKL hyperactivation. By integrating these dimensions, we provide a unified framework for CHIKV chronicity and propose targeted mitochondrial quality control as a high-value therapeutic frontier to break post-viral arthropathy.