Análise do perfil global de metilação do DNA e do promotor do fator de necrose tumoral alfa e do interferon gama em pacientes infectados pelo Dengue virus

Abstract

Dengue fever is a systemic viral infection, self-limited, transmitted to humans through the bite of infected female mosquito from Aedes genus. It is a disease with major impacts on the economy and public health, and it is estimated that between 50 to 100 million new dengue infections occur annually in more than 100 countries. Dengue fever is caused by Dengue virus (DENV), a single strand positive sense RNA virus belonging to the Flaviviridae family. The DENV infection may be asymptomatic or present different clinical manifestations, such as dengue fever (DF), hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Published data indicate that some viral infections can cause epigenetic changes in their hosts, especially in the DNA methylation. Thus, the aim of this study was to investigate the influence of DENV infection in global methylation profile of DENV infected patients by MethELISA technique, and analyze the pattern of methylation in the promoter of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) genes. The results obtained show a decrease the relative methylation percentage after DENV infection, suggesting an influence of viral infection in the epigenetic mechanisms of the host. There was also detected a higher rate of demethylation of TNF-α promoter in infected patients if compared to the control group. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-γ promoter. Meta-analysis of DNA microarray indicates that patients infected with DENV shows an increase in the expression of Thymine DNA Glycosylase (TDG) and DNA methyltransferases 1 and 3 (DNMT1 and DNMT3) genes, all involved in epigenetic regulation. So, these data indicated that DENV is able to interfere with the host epigenetic mechanisms.