Mast cells are present during the early stages of Chikungunya virus infection

Abstract

Abstract Chikungunya virus (CHIKV) is a positive-sense RNA, arthropod-borne Alphavirus. In recent years the largest recorded outbreak of CHIKV occurred in the Islands of the Indian Ocean and India. CHIKV has continued to spread causing millions of cases across more than 40 countries. Acute symptoms of infection include the abrupt onset of fever, rash, fatigue, headache, backache, and arthralgia, with arthralgia lasting up to several years in some individuals. Ongoing studies analyzing cohorts of CHIKV infected humans have led to a well-developed understanding of the clinical manifestations of CHIKV disease. What is unknown is the role different components of the immune response play in controlling CHIKV dissemination and disease development. In our current study we utilized a non-human primate (NHP) model of CHIKV infection to characterize the early stage of CHIKV infection. Adult male and female rhesus macaques (RM) were infected subcutaneously with CHIKV-LR. Analysis of vRNA loads in joint tissues of infected RM revealed that the highest viral loads were detectable at 2 dpi with at least a log decrease in vRNA levels by 7 dpi. T cells, B cells, PMNs, macrophages, and mast cells were visible in the joints of CHIKV infected RMs at 2 and 7 dpi. To our knowledge this is the first time mast cells have been identified in the tissue of CHIKV infected NHPs. Levels of key proinflammatory cytokines/chemokines were also increased from 3–7 dpi. The gene expression profile in joint tissues reveled an increase in the expression of genes involved in recruitment, activation, and maintenance of mast cells. These findings suggest that infiltration of immune cells including the newly identified mast cells from 2 to 7 dpi assist in controlling CHIKV infection.