Análise da expressão do retrovírus endógeno humano da família K (Hml-2), e da expressão de mirnas em indivíduos infectados pelo vírus da imunodeficiência humana tipo 1

• Ano de defesa: 2017
• Autor(a) principal: Ferreira, Maira Cicero [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: Herv-K; HIV-1; Mirna; Apobec
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5138389; http://repositorio.unifesp.br/handle/11600/50669

Introduction: Human Endogenous Retroviruses (HERVs) are able to modify our genetic material, because of that there are mechanisms that prevent new integrations of these elements in our genome. Studies have shown that individuals infected with Human Immunodeficiency Virus type 1 (HIV-1) have an increase in the HERV-K expression of the HML-2 subfamily, but the significance of this increase is unknown. Objectives: To evaluate the HERV-K (HML-2) expression in HIV-1 infected individuals and to investigate their possible correlation with the stage of infection. Search for miRNAs that align directly to the HERV-K genome, and cellular miRNAs that may be involved with the progression of HIV-1 infection. In addition to analyzing the expression of APOBEC3 and the action of A3G and A3F enzymes into HERV-K genome. Methodology: Performed the quantification of HERV-K (HML-2) and APOBEC3 genes. For analysis of the A3F and A3G action it was quantified the G/A hypermutations presents in the HERV-K genome. The sequenced miRNAs were analyzed using the DeSeq2 package. Results: It was observed an increase in the HERV-K (HML-2) expression in HIV-1 infected individuals, having no correlation of its expression with HIV-1 viral load, CD4+ T cell count or antiretroviral treatment. The groups with the highest HERV-K expression were those with the highest A3F expression, but there was no relation between the amount of hypermutations found in the HERV-K genome with the A3F and/or A3G expression or with the disease progression. It was not identified miRNAs that directly aligned into HERV-K genome, but it was observed that the expression of the host miRNAs allows to differentiate the individuals according to the stage of the infection. It was also observed a possible association between the miR-181a-5p expression and the host´s activation/inflammation, and of miR-150, miR-191 and miR-196a with disease progression. Conclusion: Our results confirm that the HML-2 expression is not related to any HIV-1 infection markers. In addition, it was observed a group of miRNAs that could be used to predict the progression of the disease, as well as the suggestion of using the miR-181a-5p and miR-196a-5p as markers of activation/inflammation and the rate of disease progression, respectively.