Modulação dos fatores epigenéticos nos momentos iniciais da infecção pelo HIV-1 em células T CD4+ in vitro

• Ano de defesa: 2017
• Autor(a) principal: Nunes, Jorge Meneses [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 Infection; Epigenetics; DNA methylation; Aurora kinases; CD4+ T cells; HIV-1 latency; HIV-1; Epigenética; Metilação do DNA; Aurora quinase; Células T CD4+; Latência do HIV-1
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5554589; http://repositorio.unifesp.br/handle/11600/50692

Current research trends in human immunodeficiency virus 1/acquired immune deficiency syndrome (HIV-1/AIDS) and epigenetic phenomena have been focusing on elucidating the effect of epigenetics on the viral genome and the subsequent effects on the viral life cycle, particularly during latency. However, the relationship between HIV-1 and possible epigenetic modifications of the host cell genome has not been thoroughly studied. In this context, the objective of the present study was to identify epigenetic factors that are regulated at the beginning of HIV-1 infection in activated and quiescent CD4+ T cells. We analyzed the gene and protein expression of a specific set of epigenetic targets, global DNA methylation, and HIV-1 replication kinetics for 36 hours after infecting CD4+ T cells in vitro. The cells were obtained from the blood bags of eight healthy donors. Among the 84 epigenetic targets analyzed, infection affected the expression of the genes aurora kinase B (AURKB), aurora kinase C (AURKC), and DNA methyltransferase 3B (DNMT3B). The global DNA methylation percentage exhibited opposing trends in the infected and uninfected (control) groups, increasing with time in the former and decreasing in the latter. Moreover, the detected levels of HIV-1 were higher in activated than in quiescent cells. Thus, the epigenetic targets AURKB, AURKC, and DNMT3B and the global DNA methylation profile are regulated during HIV-1 replication in CD4+ T cells, and this regulation can be influenced by the activation state of the cell at the time of infection.