Papers of the Week

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 and mice with known defects in antigen cross-presentation, accumulated in joint tissue and the spleen. Antigen-specific restimulation assays and 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 CD8α 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.CHIKV is a re-emerging mosquito-transmitted virus that in the last decade has spread into Europe, Asia, the Pacific Region, and the Americas. Joint pain, swelling and stiffness can endure for months to years after CHIKV infection, and epidemics have severe economic impact. Elucidating mechanisms by which CHIKV subverts antiviral immunity to establish and maintain a persistent infection may lead to the development of new therapeutic strategies against chronic CHIKV disease. In this study, we find that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part, by evading antiviral CD8 T cell immunity. Thus, immunomodulatory therapies that improve CD8 T cell immune surveillance and clearance of CHIKV infection could be a strategy for mitigating chronic CHIKV disease.