Systems analysis of subjects acutely infected with the Chikungunya virus

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...

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Veröffentlicht in:	PLoS pathogens Jg. 15; H. 6; S. e1007880
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 01.06.2019 Public Library of Science (PLoS)
Schlagworte:	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
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Zusammenfassung:	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.
Bibliographie:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1007880