RESUMO
Several factors are involved in the control of HIV transcription/replication, including epigenetic modifications at the promoter level. Analysis of the HIV long terminal repeat (LTR) methylation status in infected patients controlling viremia is scarce. Herein, we show a higher degree of DNA methylation in the 5'-LTR of long-term nonprogressor and elite controller (LTNP/EC) versus progressor patients and a positive correlation with time of infection, indicating a certain contribution of HIV LTR silencing in reducing the number of replicating viruses which may account for a delayed progression.
Assuntos
Metilação de DNA , Epigênese Genética/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Viremia/prevenção & controle , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/sangue , Repetição Terminal Longa de HIV/genética , Sobreviventes de Longo Prazo ao HIV , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Filogenia , Provírus/genética , Viremia/genéticaRESUMO
INTRODUCTION: In HIV-positive individuals, complex multifactorial mechanisms control viral infection. In addition to viral and immunological factors, the host genetic background also plays an important role. Our objective was to evaluate how various genetic factors associated with delayed AIDS onset. METHODS: Thirty HIV+ long-term nonprogressors (LTNPs) and 30 known progressors were analyzed. Host genes were analyzed in peripheral blood mononuclear cells DNA: CCR5 and HLA were polymerase chain reaction typed. HLA-C5', HCP5 polymorphisms, and CCL3L1 copy number were determined using real-time polymerase chain reaction. RESULTS: The CCL3L1high-copy-CCR5 deletion genetic risk groups was overrepresented in LTNPs. However, separately, neither CCL3L1 nor CCR5 were significantly associated with clinical outcome. HLA seemed as a strong nonprogression determinant, mainly HLA-B and the less-studied HLA-C. HLA-Cw0102 and HLA-C5' had an impact on LTNP phenotype along with HLA-B5701 and B2705. The presence of allele combinations like HLA- B*5701-Cw0602, HLA-B*2705-Cw0102, or HLA-B*3801-Cw1203 had the strongest effect in non-progression. As for HCP5, no independent effect was observed. The studied factors had additive effects, and although the number of patients was small, it seemed that carrying a high number of protective alleles associated with progression delay. CONCLUSIONS: We showed the additive load of protective host factors was predictive of nonprogression, and that HLA-associated factors were predominant in this global effect.