Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response

Author:

Mantovani Nathalia,Defelicibus Alexandre,da Silva Israel Tojal,Cicero Maira Ferreira,Santana Luiz Claudio,Arnold Rafael,de Castro Daniela Funayama,Duro Rodrigo Lopes Sanz,Nishiyama-Jr Milton Yutaka,Junqueira-de-Azevedo Inácio Loiola Meirelles,da Silva Bosco Christiano Maciel,da Silva Duarte Alberto José,Casseb Jorge,de Barros Tenore Simone,Hunter James,Diaz Ricardo Sobhie,Komninakis Shirley Cavalcante Vasconcelos

Abstract

AbstractDNA methylation is one of the epigenetic modifications that configures gene transcription programs. This study describes the DNA methylation profile of HIV-infected individuals with distinct characteristics related to natural and artificial viremia control. Sheared DNA from circulating mononuclear cells was subjected to target enrichment bisulfite sequencing designed to cover CpG-rich genomic regions. Gene expression was assessed through RNA-seq. Hypermethylation in virologic responders was highly distributed closer to Transcription Start Sites (p-value = 0.03). Hyper and hypomethylation levels within TSS adjacencies varied according to disease progression status (Kruskal–Wallis, p < 0.001), and specific differentially methylated regions associated genes were identified for each group. The lower the promoter methylation, the higher the gene expression in subjects undergoing virologic failure (R = − 0.82, p = 0.00068). Among the inversely correlated genes, those supporting glycolysis and its related pathways were hypomethylated and up-regulated in virologic failures. Disease progression heterogeneity was associated with distinct DNA methylation patterns in terms of rates and distribution. Methylation was associated with the expression of genes sustaining intracellular glucose metabolism in subjects undergoing antiretroviral virologic failure. Our findings highlight that DNA methylation is associated with latency, disease progression, and fundamental cellular processes.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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