Demethylation profile of the TNF-α promoter gene is associated with high expression of this cytokine in Dengue virus patients

• Published in: Journal of medical virology Vol. 88; no. 8; pp. 1297 - 1302
• Main Authors: Gomes, Alessandra Vilas Boas Terra, de Souza Morais, Stella Maria, Menezes-Filho, Sergio Luiz, de Almeida, Luiz Gustavo Nogueira, Rocha, Raissa Prado, Ferreira, Jaqueline Maria Siqueira, dos Santos, Luciana Lara, Malaquias, Luiz Cosme Cotta, Coelho, Luiz Felipe Leomil
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-08-2016
• Subjects: Adult; CpG Islands; Dengue - genetics; Dengue - immunology; Dengue virus; Dengue Virus - immunology; DNA Methylation; Female; Humans; IFN-γ; Interferon-gamma - genetics; Interferon-gamma - immunology; Male; Middle Aged; Polymerase Chain Reaction; promoter; Promoter Regions, Genetic; RNA, Viral - blood; RNA, Viral - isolation & purification; TNF-α; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Young Adult; DNA methylation; IFN-γ; promoter; TNF-α; Dengue virus
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.24478

Dengue is the most prevalent arthropod‐borne viral illness in humans. The overexpression of cytokines by Dengue virus (DENV) infected cells is associated with the most severe forms of the disease. Unmethylated CpG islands are related to a transcriptionally active structure, whereas methylated DNA recruits methyl‐binding proteins that inhibit gene expression. Several studies have described the importance of epigenetic events in the regulation and expression of many cytokines. The purpose of the present study was to evaluate the methylation status of the IFN‐γ and TNF‐α promoters in DNA extracted from dengue infected patients using methylation‐specific polymerase chain reaction. A high frequency of demethylation was observed in the TNF‐α promoter of DENV infected patients when compared to non‐infected controls. The patients with an unmethylated profile showed higher expression of TNF‐α mRNA than patients with the methylated status. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN‐γ promoter or in the expression of IFN‐γ transcripts. The present study provides the first association of TNF‐α promoter demethylation in DENV infected individuals and demonstrates a correlation between the methylation status of the region analyzed and the expression of TNF‐α transcripts in DENV infected patients. J. Med. Virol. 88:1297–1302, 2016. © 2016 Wiley Periodicals, Inc.