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PLoS Pathog. 2019 Jun 18;15(6):e1007880. doi: 10.1371/journal.ppat.1007880. eCollection 2019 Jun.

Systems analysis of subjects acutely infected with the Chikungunya virus.

Author information

1
Bacteriology Laboratory, Butantan Institute, São Paulo, Brazil.
2
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
3
Departamento de Biologia Celular, Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
4
Health Foundation Parreiras Horta, Central Laboratory of Public Health (LACEN/SE), State Secretary for Health, Sergipe, Brazil.
5
Special Laboratory for Applied Toxinology, Butantan Institute, São Paulo, Brazil.
6
Respiratory Diseases Division, Virology Center, Adolfo Lutz Institute, Sao Paulo, Brazil.
7
Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
8
Division of Immunology and Molecular Biology Laboratory, University Hospital/EBSERH, Federal University of Sergipe, Sergipe, Brazil.
9
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
10
Bacteriology Service, Bioindustrial Division, Butantan Institute, São Paulo, Brazil.
11
Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Abstract

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

Conflict of interest statement

The authors have declared that no competing interests exist.

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