TY - JOUR T1 - Systems Analysis of Subjects Acutely Infected with Chikungunya Virus JF - bioRxiv DO - 10.1101/531921 SP - 531921 AU - Alessandra Soares-Schanoski AU - Natália Baptista Cruz AU - Luíza Antunes de Castro-Jorge AU - Renan Villanova Homem de Carvalho AU - Cliomar Alves dos Santos AU - Nancy da Rós AU - Úrsula Oliveira AU - Danuza Duarte Costa AU - Cecília Luíza Simões dos Santos AU - Marielton dos Passos Cunha AU - Maria Leonor Sarno Oliveira AU - Juliana Cardoso Alves AU - Regina Adalva de Lucena Couto Océa AU - Danielle Rodrigues Ribeiro AU - André Nicolau Aquime Gonçalves AU - Patricia Gonzalez AU - Andreas Suhrbier AU - Paolo Marinho de Andrade Zanotto AU - Inácio Junqueira de Azevedo AU - Dario S. Zamboni AU - Roque Pacheco Almeida AU - Paulo Lee Ho AU - Jorge Kalil AU - Milton Yutaka Nishiyama, Junior AU - Helder I Nakaya Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/28/531921.abstract N2 - The largest ever recorded epidemic of the chikungunya virus (CHIKV) began 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 used to analyze the blood transcriptomes of adults acutely infected with CHIKV. Gene signatures that were associated with viral RNA amounts and to the onset of symptoms were identified. Among those genes, the putative role of 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 those induced by dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that CHIKV infection in mice induced IL-1 beta production in a mechanism highly dependent on the inflammasome NLRP3 activation. The findings provided valuable insights into the virus–host interactions during the acute phase and could be useful in the investigation of new and effective therapeutic interventions. ER -