Systems analysis of subjects acutely infected with the Chikungunya virus

• Published in: PLoS pathogens Vol. 15; no. 6; p. e1007880
• Main Authors: Soares-Schanoski, Alessandra, Baptista Cruz, Natália, de Castro-Jorge, Luíza Antunes, de Carvalho, Renan Villanova Homem, Santos, Cliomar Alves dos, Rós, Nancy da, Oliveira, Úrsula, Costa, Danuza Duarte, Santos, Cecília Luíza Simões dos, Cunha, Marielton dos Passos, Oliveira, Maria Leonor Sarno, Alves, Juliana Cardoso, Océa, Regina Adalva de Lucena Couto, Ribeiro, Danielle Rodrigues, Gonçalves, André Nicolau Aquime, Gonzalez-Dias, Patricia, Suhrbier, Andreas, Zanotto, Paolo Marinho de Andrade, Azevedo, Inácio Junqueira de, Zamboni, Dario S., Almeida, Roque Pacheco, Ho, Paulo Lee, Kalil, Jorge, Nishiyama, Milton Yutaka, Nakaya, Helder I.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2019; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Animals; Apolipoprotein B; Apolipoproteins; Arthritis; Arthritis - immunology; Arthritis - pathology; Arthritis - virology; Bacteriology; Bioinformatics; Biology and life sciences; Bone marrow; Care and treatment; Catalysis; Chikungunya Fever - immunology; Chikungunya Fever - pathology; Chikungunya virus; Chikungunya virus - physiology; Computer and Information Sciences; Cytidine Deaminase - immunology; Cytokines; Dengue; Dengue fever; Dengue virus; Dengue Virus - immunology; Dengue Virus - pathogenicity; Epidemics; Epidemiology; Female; Fever; Fever - immunology; Fever - pathology; Fever - virology; Follow-Up Studies; Funding; Gene expression; Genes; Genomes; Hospitals; Humans; Immunology; Infection; Infections; Inflammasomes; Interleukin 1; Interleukin-1beta - immunology; Laboratories; Macrophages; Medical research; Medicine and Health Sciences; Messenger RNA; Mice; Molecular biology; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; Pharmaceutical sciences; Polyarthritis; Proteins - immunology; Public health; Rheumatoid arthritis; Rheumatoid factor; Risk factors; RNA; RNA editing; Signatures; Signs and symptoms; Software; Supervision; Systems analysis; Therapeutic applications; Vector-borne diseases; Viral diseases; Virology; Virus diseases; Virus Replication - immunology; Viruses; Africa; Brazil; India
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007880

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.