Demethylation Profile of the TNF-alpha Promoter Gene Is Associated With High Expression of This Cytokine in Dengue virus Patients

作者：Boas Terra Gomes Alessandra Vilas; de Souza Morais Stella Maria; Menezes Filho Sergio Luiz; Nogueira de Almeida Luiz Gustavo; Rocha Raissa Prado; Siqueira Ferreira Jaqueline Maria; dos Santos Luciana Lara; Cotta Malaquias Luiz Cosme; Leomil Coelho Luiz Felipe

来源：Journal of Medical Virology, 2016, 88(8): 1297-1302.

DOI：10.1002/jmv.24478

• Dengue virus
• DNA methylation
• promoter
• IFN-gamma
• TNF-alpha

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-gamma and TNF-alpha promoters in DNA extracted from dengue infected patients using methylation-specific polymerase chain reaction. A high frequency of demethylation was observed in the TNF-alpha promoter of DENV infected patients when compared to non-infected controls. The patients with an unmethylated profile showed higher expression of TNF-alpha mRNA than patients with the methylated status. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-gamma promoter or in the expression of IFN-gamma transcripts. The present study provides the first association of TNF-alpha promoter demethylation in DENV infected individuals and demonstrates a correlation between the methylation status of the region analyzed and the expression of TNF-alpha transcripts in DENV infected patients.

• 出版日期2016-8