Alterações epigenéticas em pacientes infectados pelo vírus da imunodeficiência humana-1

• Ano de defesa: 2016
• Autor(a) principal: Pena, Nathalia Mantovani [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: HIV-1; Metilação; Epigenética; Sequenciamento de nova geração
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3890539; http://repositorio.unifesp.br/handle/11600/48584

Introduction: DNA methylation is one of the major mechanisms that regulates gene expression in the cell enviroment. Exogenous factors, such as viral infection, may compromise the regulation of the gene expression and destabilize this process. Therefore, we conducted the analysis of the cytosine methylation profile in HIV-1 infected patients and analyzed if the change in the methylation profile was correlated with gene expression. Methods: Methylation analysis were performed in 28 individuals, six HIV negative controls and 22 HIV patients who showed different rate of clinical progression. In order to perform Methyl-Seq, the libraries were prepared using the SureSelect Methyl-Seq target enrichment system kit for multiplexed Illumina sequencing and sequenced in the Hiseq 1000 Illumina platform. The transcriptome was analyzed in 15 individuals, six controls and nine HIV patients. In order to perform RNA-Seq libraries, we used the Truseq Stranded mRNA Sample Prep Kit and the Libraries in the Hiseq 2500 Illumina platform. Results: According to the analysis, 5,471 regions nearby or within genes were differentially methylated. The HDAC4 gene presented a hypermethylated region that varied significantly among the different groups of subjects. Individuals that exhibit a spontaneous control of the HIV infection, showed a lower level of methylation in HDAC4 gene compared to those who control the infection under antiretroviral treatment. The HIST1H3J and eEF2 genes were significantly hiypomethylated in the HIV infected individuals. Discussion: HDAC4 plays an important role in histone deacetylation. HDAC4 may participate in the virus silencing process and may be related to the persistence of the HIV infection. The eEF2 protein is essential for the translation elongation, and possibly participate in the process of stress granules inhibition promoted by the virus. However, no such genes were found differentially expressed in the samples. Conclusion: According to the results, the HIV infection may alter the methylation profile in the human genome. The change in the methylation status can be promoted by the virus or by the cell in response to the infection and may compromise important cellular process.