Systems analysis of subjects acutely infected with the Chikungunya virus

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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]

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^[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

• Tipo de documento: Artigo Científico
• Fonte: PLOS PATHOGENS; v. 15, n. 6 JUN 2019.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 12/19278-6 - Biologia de sistemas de longos RNAs não-codificadores
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/25055-8 - Humanização do sistema de glicosilação de Pichia Pastoris pela técnica CRISPR-Cas9 visando a expressão de proteínas recombinantes terapêuticas
• Beneficiário: Paulo Lee Ho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/08204-2 - Diversidade genética e filodinâmica dos arbovírus emergentes e reemergentes (DENV, ZIKV e CHIKV) nas regiões Nordeste e Sudeste do Brasil, 2014-2016
• Beneficiário: Marielton dos Passos Cunha
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/50137-3 - Long noncoding RNA interplay with the host microbiome may determine mucosal influenza vaccine immunogenicity
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Regular