UNDERSTANDING CHIKUNGUNYA VIRUS PATHOGENESIS AND IMMUNE REGULATION AS THERAPY

Abstract

Chikungunya fever (CHIKF) is a febrile disease with debilitating rheumatic manifestation caused by the chikungunya virus (CHIKV). Since a re-emergence in 2006, global incidence of CHIKF has been increasing rapidly. Despite this worrying trend, no licensed vaccine or targeted treatment is available. At the beginning of this study, efforts to characterize a juvenile mouse model of CHIKV infection was made as we observed a marked difference in immune response between juvenile mice with age of one week apart. Using the established juvenile mouse model, depletion of regulatory T cells (Tregs) was found to exacerbate disease pathology. Acute loss of Tregs resulted in severe immunopathology and increased viremia with long term sequelae. Expansion of Tregs with prophylactic adminstration of agonistic IL-2 antibody complex (IL-2 Ab Cx) protects mice against CHIKV-induced pathology without affecting virus clearance. Finally, therapeutic use of IL-2 Ab Cx during active virus infection was explored with pathogenic outcome.