Chikungunya virus evades antiviral CD8⁺ T cell responses to establish persistent infection in joint-associated tissues.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes explosive epidemics of a febrile illness characterized by debilitating arthralgia and arthritis and can endure for months to years following infection. In mouse models, CHIKV persists in joint tissues for weeks to months and is associated with chronic synovitis. Using a recombinant CHIKV strain encoding a CD8+ T cell receptor epitope from ovalbumin, as well as a viral peptide-specific MHC class I tetramer, we interrogated CD8+ T cell responses during CHIKV infection. Epitope-specific CD8+ T cells, which were reduced in Batf3-/- and Wdfy4-/- mice with known defects in antigen cross-presentation, accumulated in joint tissue and the spleen. Antigen-specific ex vivo restimulation assays and in vivo killing assays demonstrated that CD8+ T cells produce cytokine and have cytolytic activity. Despite the induction of a virus-specific CD8+ T cell response, CHIKV burden in joint-associated tissues and the spleen were equivalent in wild-type (WT) and CD8a-/- mice during both the acute and chronic phases of infection. In comparison, CD8+ T cells were essential for control of acute and chronic lymphocytic choriomeningitis virus in the joint and spleen. Moreover, adoptive transfer of virus-specific effector CD8+ T cells, or immunization with a vaccine that induces virus-specific effector CD8+ T cells, prior to infection enhanced clearance of CHIKV infection in the spleen, but had minimal impact on CHIKV infection in the joint. Collectively, these data suggest that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part, by evading CD8+ T cell immunity. [ABSTRACT FROM AUTHOR]

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