Abstract
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.
Publication types
-
Clinical Trial
-
Multicenter Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Animals
-
Arthritis / immunology*
-
Arthritis / pathology
-
Arthritis / virology
-
Chikungunya Fever / immunology*
-
Chikungunya Fever / pathology
-
Chikungunya virus / physiology*
-
Cytidine Deaminase / immunology*
-
Dengue Virus / immunology
-
Dengue Virus / pathogenicity
-
Female
-
Fever / immunology
-
Fever / pathology
-
Fever / virology
-
Follow-Up Studies
-
Humans
-
Interleukin-1beta / immunology
-
Mice
-
NLR Family, Pyrin Domain-Containing 3 Protein / immunology
-
Proteins / immunology*
-
Virus Replication / immunology*
Substances
-
IL1B protein, human
-
Interleukin-1beta
-
NLR Family, Pyrin Domain-Containing 3 Protein
-
NLRP3 protein, human
-
Proteins
-
APOBEC3A protein, human
-
Cytidine Deaminase
Grants and 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.