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Title: Analysis of the immunological biomarker profile during acute zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage
Authors: 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 Souza
Amaral, L. Rodrigues
Campi-Azevedo, Ana Carolina
Coelho-Dos-Reis, Jordana Grazziela Alves
Antonelli, Lis R.
Teixeira-Carvalho, Andréa
Martins-Filho, Olindo Assis
Ramasawmy, Rajendranath
Keywords: Biological Marker
Gamma Interferon Inducible Protein 10
Acute Disease
Case Control Study
Cross-sectional Study
Gene Expression
Middle Aged
Zika Fever
Acute Disease
Case-control Studies
Chemokine Cxcl10
Cross-sectional Studies
Gene Expression
Middle Aged
Zika Virus Infection
Issue Date: 2018
metadata.dc.publisher.journal: Memórias do Instituto Oswaldo Cruz
metadata.dc.relation.ispartof: Volume 113, Número 6
Abstract: 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. © 2018, Fundacao Oswaldo Cruz. All rights reserved.
metadata.dc.identifier.doi: 10.1590/0074-02760170542
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