Systems analysis of subjects acutely infected with the Chikungunya virus

Author(s):Show less -

Soares-Schanoski, Alessandra ^[1] ; Baptista Cruz, Natalia ^[2] ; de Castro-Jorge, Luiza Antunes ^[3] ; Homem de Carvalho, Renan Villanova ^[3] ; dos Santos, Cliomar Alves ^[4] ; da Ros, Nancy ^[5] ; Oliveira, Ursula ^[5] ; Costa, Danuza Duarte ^[4] ; Simoes dos Santos, Cecilia Luiza ^[6] ; Cunha, Marielton dos Passos ^[7] ; Sarno Oliveira, Maria Leonor ^[1] ; Alves, Juliana Cardoso ^[8] ; de Lucena Couto Ocea, Regina Adalva ^[8] ; Ribeiro, Danielle Rodrigues ^[8] ; Aquime Goncalves, Andre Nicolau ^[2] ; Gonzalez-Dias, Patricia ^[2] ; Suhrbier, Andreas ^[9] ; de Andrade Zanotto, Paolo Marinho ^[7] ; de Azevedo, Inacio Junqueira ; Zamboni, Dario S. ^[3] ; Almeida, Roque Pacheco ; Ho, Paulo Lee ^[10] ; Kalil, Jorge ^[11] ; Nishiyama, Milton Yutaka ^[5] ; Nakaya, Helder I. ^[2]

Affiliation:Show less -

^[1] Butantan Inst, Bacteriol Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular Mol & Bioagentes Patogen, Ribeirao Preto - Brazil

^[4] State Secretary Hlth, Cent Lab Publ Hlth LACEN SE, Hlth Fdn Parreiras Horta, Sergipe - Brazil

^[5] Butantan Inst, Special Lab Appl Toxinol, Sao Paulo - Brazil

^[6] Adolfo Lutz Inst, Virol Ctr, Resp Dis Div, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Biomed Sci Inst, Dept Microbiol, Lab Mol Evolut & Bioinformat, Sao Paulo - Brazil

^[8] Univ Fed Sergipe, Univ Hosp EBSERH, Div Immunol & Mol Biol Lab, Sergipe - Brazil

^[9] QIMR Berghofer Med Res Inst, Brisbane, Qld - Australia

^[10] Butantan Inst, Bioind Div, Bacteriol Serv, Sao Paulo - Brazil

^[11] Univ Sao Paulo, Fac Med, Heart Inst, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLOS PATHOGENS; v. 15, n. 6 JUN 2019.
• Web of Science Citations: 4

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. Author summary 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. (AU)

• FAPESP's process: 12/19278-6 - Systems biology of long non-coding RNAs
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/25055-8 - Humanization of the glycosylation system of Pichia Pastoris via CRISPR-Cas9 technique aiming the expression of therapeutical recombinant proteins
• Grantee: Paulo Lee Ho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/08204-2 - Genetic and phylodynamics diversity of emerging and re-emerging arboviruses (DENV, ZIKV and CHIKV) in the Northeast and Southeast regions of Brazil, 2014-2016
• Grantee: Marielton dos Passos Cunha
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/50137-3 - Long noncoding RNA interplay with the host microbiome may determine mucosal influenza vaccine immunogenicity
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Regular Research Grants