ROWING AGAINST THE TIDE: Decrease inflammatory markers during viremic Chikungunya asymptomatic infection
RNA-seq; autoimmune disease, granzyme, Chikungunya virus, acute viral infection, viral pathogenesis
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which has emerged or reemerged in the last twenty years. CHIKV infection causes varied outcomes including asymptomatic infection, mild disease or severe disease with debilitating arthritis. The purpose of the current study was to discover immune pathways associated with different outcomes of CHIKV infection by transcriptional profiling of whole blood from CHIKV-infected individuals. During the 2016 CHIKV outbreak in Brazil, whole blood samples were collected from CHIKV-infected individuals diagnosed by RT-qPCR or neutralization assays, and control, non-infected individuals. Among the collected samples, 4 were in the acute phase, 6 had recovered or mild symptoms, and 2 were asymptomatic. RNAseq was performed on RNA from whole blood cells, and sequenced fragments were mapped by alignment to the human or to the CHIKV genomes.Libraries had a mean of 96% of transcripts mapping to the human genome, and 3 from acute subjects contained sequences mapping to the CHIKV genome. There was a mean of 490, 1463 and 370 differentially expressed genes (DEGs) between Asymptomatic, Acute, and Non-Acute transcriptomes, respectively. DEGs from the Acute group were highly associated with type I interferon response with upregulation of STAT1, STAT2and a series of other interferon-stimulated genes (ISGs) such as RSDA2and IRF7. Asymptomatic viremic CHIKV subjects, in contrast, had decreased ISG signatures and granzyme A (GZMA) compared to controls.Whole blood cells from subjects with symptomatic CHIKV infection expressed transcriptional profiles gene pathways similar to those expressed during autoimmune disease. In contrast, asymptomatic subjects had suppressed GZMA but unchanged ISG expression. These findings suggest that an inflammatory state is present during acute symptomatic CHIKV infection, whereas there is a decrease in inflammatory markers during asymptomatic infection.