Identification of the T cell receptor (TCR) repertoire associated with sustained joint pains in chronic chikungunya virus disease

Chikungunya virus (CHIKV) is a reemerging human pathogen that has seen a rapid global spread in the past decade. It is the most wide-spread member of a group of mosquito transmitted, arthritogenic viruses that can leave up to half of the patients with chronic joint pains long after the initial infection. The chronic joint pain is caused by sustained inflammation and bears hallmarks of auto-immune rheumatoid arthritis. However, the antigenic driver of the prolonged joint inflammation, and the relative contribution of auto-reactive immune cells have not been elucidated. Using next-gen T-cell Receptor (TCR) sequencing on peripheral blood CD4 T cells from CHIKV patients that do or do not develop sustained joint pains we will identify the TCR signatures specifically associated with development of chronic disease. These preliminary findings will extend the role of T cells in the etiology of chronic CHIKV to humans, provide a basis for the search for the antigenic drivers of the disease and potentially identify biomarkers for progression to chronic CHIKV.

Chikungunya virus (CHIKV) is a reemerging human pathogen that has seen a rapid global spread in the past decade. It is the most wide-spread member of a group of mosquito transmitted, arthritogenic viruses that can leave up to half of the patients with chronic joint pains long after the initial infection. The chronic joint pain is caused by sustained inflammation and bears hallmarks of auto-immune rheumatoid arthritis. However, the antigenic driver of the prolonged joint inflammation, and the relative contribution of auto-reactive immune cells have not been elucidated. Using next-gen T-cell Receptor (TCR) sequencing on peripheral blood CD4 T cells from CHIKV patients that do or do not develop sustained joint pains we will identify the TCR signatures specifically associated with development of chronic disease. These preliminary findings will extend the role of T cells in the etiology of chronic CHIKV to humans, provide a basis for the search for the antigenic drivers of the disease and potentially identify biomarkers for progression to chronic CHIKV.