Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Memórias do Instituto Oswaldo Cruz |
Texto Completo: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000600303 |
Resumo: | BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application. |
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Memórias do Instituto Oswaldo Cruz |
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Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damageZika virusCXCL10biomarkerschemokinescytokines BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.Instituto Oswaldo Cruz, Ministério da Saúde2018-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000600303Memórias do Instituto Oswaldo Cruz v.113 n.6 2018reponame:Memórias do Instituto Oswaldo Cruzinstname:Fundação Oswaldo Cruzinstacron:FIOCRUZ10.1590/0074-02760170542info:eu-repo/semantics/openAccessNaveca,Felipe GomesPontes,Gemilson SoaresChang,Aileen Yu-henSilva,George Allan Villarouco daNascimento,Valdinete Alves doMonteiro,Dana Cristina da SilvaSilva,Marineide Souza daAbdalla,Lígia FernandesSantos,João Hugo AbdallaAlmeida,Tatiana Amaral Pires deMejía,Matilde del Carmen ContrerasMesquita,Tirza Gabrielle Ramos deEncarnação,Helia Valeria de SouzaGomes,Matheus de SouzaAmaral,Laurence RodriguesCampi-Azevedo,Ana CarolinaCoelho-dos-Reis,Jordana GrazielaAntonelli,Lis Ribeiro do ValeTeixeira-Carvalho,AndréaMartins-Filho,Olindo AssisRamasawmy,Rajendranatheng2020-04-25T17:52:52Zhttp://www.scielo.br/oai/scielo-oai.php0074-02761678-8060opendoar:null2020-04-26 02:22:12.728Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruztrue |
dc.title.none.fl_str_mv |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
title |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
spellingShingle |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage Naveca,Felipe Gomes Zika virus CXCL10 biomarkers chemokines cytokines |
title_short |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
title_full |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
title_fullStr |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
title_full_unstemmed |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
title_sort |
Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage |
author |
Naveca,Felipe Gomes |
author_facet |
Naveca,Felipe Gomes Pontes,Gemilson Soares Chang,Aileen Yu-hen Silva,George Allan Villarouco da Nascimento,Valdinete Alves do Monteiro,Dana Cristina da Silva Silva,Marineide Souza da Abdalla,Lígia Fernandes Santos,João Hugo Abdalla Almeida,Tatiana Amaral Pires de Mejía,Matilde del Carmen Contreras Mesquita,Tirza Gabrielle Ramos de Encarnação,Helia Valeria de Souza Gomes,Matheus de Souza Amaral,Laurence Rodrigues Campi-Azevedo,Ana Carolina Coelho-dos-Reis,Jordana Graziela Antonelli,Lis Ribeiro do Vale Teixeira-Carvalho,Andréa Martins-Filho,Olindo Assis Ramasawmy,Rajendranath |
author_role |
author |
author2 |
Pontes,Gemilson Soares Chang,Aileen Yu-hen Silva,George Allan Villarouco da Nascimento,Valdinete Alves do Monteiro,Dana Cristina da Silva Silva,Marineide Souza da Abdalla,Lígia Fernandes Santos,João Hugo Abdalla Almeida,Tatiana Amaral Pires de Mejía,Matilde del Carmen Contreras Mesquita,Tirza Gabrielle Ramos de Encarnação,Helia Valeria de Souza Gomes,Matheus de Souza Amaral,Laurence Rodrigues Campi-Azevedo,Ana Carolina Coelho-dos-Reis,Jordana Graziela Antonelli,Lis Ribeiro do Vale Teixeira-Carvalho,Andréa Martins-Filho,Olindo Assis Ramasawmy,Rajendranath |
author2_role |
author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Naveca,Felipe Gomes Pontes,Gemilson Soares Chang,Aileen Yu-hen Silva,George Allan Villarouco da Nascimento,Valdinete Alves do Monteiro,Dana Cristina da Silva Silva,Marineide Souza da Abdalla,Lígia Fernandes Santos,João Hugo Abdalla Almeida,Tatiana Amaral Pires de Mejía,Matilde del Carmen Contreras Mesquita,Tirza Gabrielle Ramos de Encarnação,Helia Valeria de Souza Gomes,Matheus de Souza Amaral,Laurence Rodrigues Campi-Azevedo,Ana Carolina Coelho-dos-Reis,Jordana Graziela Antonelli,Lis Ribeiro do Vale Teixeira-Carvalho,Andréa Martins-Filho,Olindo Assis Ramasawmy,Rajendranath |
dc.subject.por.fl_str_mv |
Zika virus CXCL10 biomarkers chemokines cytokines |
topic |
Zika virus CXCL10 biomarkers chemokines cytokines |
dc.description.none.fl_txt_mv |
BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application. |
description |
BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000600303 |
url |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000600303 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/0074-02760170542 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Instituto Oswaldo Cruz, Ministério da Saúde |
publisher.none.fl_str_mv |
Instituto Oswaldo Cruz, Ministério da Saúde |
dc.source.none.fl_str_mv |
Memórias do Instituto Oswaldo Cruz v.113 n.6 2018 reponame:Memórias do Instituto Oswaldo Cruz instname:Fundação Oswaldo Cruz instacron:FIOCRUZ |
reponame_str |
Memórias do Instituto Oswaldo Cruz |
collection |
Memórias do Instituto Oswaldo Cruz |
instname_str |
Fundação Oswaldo Cruz |
instacron_str |
FIOCRUZ |
institution |
FIOCRUZ |
repository.name.fl_str_mv |
Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruz |
repository.mail.fl_str_mv |
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