Research Article: Systems analysis of subjects acutely infected with the Chikungunya virus

Date Published: June 18, 2019

Publisher: Public Library of Science

Author(s): Alessandra Soares-Schanoski, Natália Baptista Cruz, Luíza Antunes de Castro-Jorge, Renan Villanova Homem de Carvalho, Cliomar Alves dos Santos, Nancy da Rós, Úrsula Oliveira, Danuza Duarte Costa, Cecília Luíza Simões dos Santos, Marielton dos Passos Cunha, Maria Leonor Sarno Oliveira, Juliana Cardoso Alves, Regina Adalva de Lucena Couto Océa, Danielle Rodrigues Ribeiro, André Nicolau Aquime Gonçalves, Patricia Gonzalez-Dias, Andreas Suhrbier, Paolo Marinho de Andrade Zanotto, Inácio Junqueira de Azevedo, Dario S. Zamboni, Roque Pacheco Almeida, Paulo Lee Ho, Jorge Kalil, Milton Yutaka Nishiyama, Helder I. Nakaya, David H O’Connor.


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.

Partial Text

The Chikungunya virus (CHIKV) is a mosquito-borne reemerging arbovirus responsible for intermittent and devastating outbreaks [1]. The largest epidemic of CHIKV ever recorded started in Africa in 2004 and has spread globally, reaching the Americas in 2014. The disease has afflicted four continents, affected more than 100 countries and infected over 10 million people [2, 3]. Its global impact is still growing [4]. CHIKV has spread rapidly through several Brazilian states and infected a total of 20,598 individuals in 2015 [5]; furthermore, more than 200,000 suspected cases were reported in 2017–2018 [6].

CHIKV re-emergence in the past 15 years has led to major epidemic outbreaks in Asia, Africa, the Indian Ocean and more recently in the Americas after decades of intermittent outbreaks [48]. Despite considerable progress in understanding the infection, much of the host-pathogen interplay remains obscure.




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