Nadando contra a corrente: diminuição dos marcadores inflamatórios em pessoas assintomáticas infectadas pelo vírus Chikungunya

Abstract

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, causing an increase in disability-adjusted life-years (DALY). 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 from control, non-infected individuals. Among the collected samples, four were from patients in the acute phase, six from recovered or mild symptoms ones, and two were asymptomatic. From whole blood cells extracted RNA, we performed an RNASeq analysis and mapped the sequenced fragments to the human or 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 strongly associated with type I interferon response with upregulation of STAT1, STAT2 and a series of other interferon-stimulated genes (ISGs) such as RSDA2 and IRF7. The number of ISGs differentially expressed by the group of people with asymptomatic infection is reduced, which may be related to a weak response by type I interferon. Another highlight among the set of DEGs of asymptomatic people is the underexpression of the coding gene of the protein Granzima A (GZMA), one of the main promoters of inflammation in arthritis. The enrichment analyzes with Gene Ontology terms, using DEGs, showed that the group of people in the acute phase of the disease had high expression in genes related to the process of elimination of the virus, inflammatory response and control of cell replication. An Ingenuity Pathway Analysis functional enrichment analysis showed that GDEs in the asymptomatic group of people are involved in suppressing leukocyte activation and decreasing cell movement of monocytes and leukocytes. Our findings suggest that an inflammatory state is present during acute symptomatic CHIKV infection, while there is a decrease in these markers during asymptomatic infection