[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Systems analysis of subjects acutely infected with the Chikungunya virus
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, [ … ], Helder I. Nakaya
Published: June 18, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1007880 / This is an uncorrected proof.
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.
The Chikungunya virus (CHIKV) has infected millions of people worldwide and presents a serious public health issue. Acute symptomatic infections caused by contracting this mosquito-transmitted arbovirus are typically associated with an abrupt onset of fever and often debilitating polyarthralgia/ polyarthritis, as well as prolonged periods of disability in some patients. These dramatic effects call for a careful evaluation of the molecular mechanisms involved in this puzzling infection. By analyzing the blood transcriptome of adults acutely infected with CHIKV, we were able to provide a detailed picture of the early molecular events induced by the infection. Additionally, the systems biology approach revealed genes that can be investigated extensively as probable therapeutic targets for the disease.
Citation: Soares-Schanoski A, Baptista Cruz N, de Castro-Jorge LA, de Carvalho RVH, Santos CAd, Rós Nd, et al. (2019) Systems analysis of subjects acutely infected with the Chikungunya virus. PLoS Pathog 15(6): e1007880. https://doi.org/10.1371/journal.ppat.1007880
Editor: David H. O’Connor, University of Wisconsin, UNITED STATES
Received: February 1, 2019; Accepted: May 30, 2019; Published: June 18, 2019
Copyright: © 2019 Soares-Schanoski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All RNA-seq raw data is available at the NCBI in BioProject: PRJNA507472 and the BioSample Range from SAMN10847030 to SAMN10847088
Funding: H.I.N. is supported by the São Paulo Research Foundation (FAPESP; grants 2017/50137-3, 2012/19278-6, and 2013/08216-2). A.S.S. is supported by Butantan Foundation, CNPq (Grant 443371/2016-4) and Brazilian Health Ministry. R.A. is supported by FINEP Grant 0116005600. D.R.R. has a postdoctoral fellowship from CNPq. J.C.A. has a postdoctoral fellowship from CAPES – Finance Code 001. M.P.C. has a PhD fellowship from FAPESP – 2016/08204-2. I.J.A is supported by São Paulo Research Foundation (FAPESP; grant: CEPID 2013/07467-1). P.L.H is supported by Butantan Foundation, CNPq 306992/2014-0 and Fapesp 2015/25055-8. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Keywords: Chikungunya fever, Viral pathogenesis.