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

• Published in: Scientific reports Vol. 11; no. 1; pp. 22993 - 15
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/2210; 631/208/176/1988; 631/250/255/1901; 631/250/255/2514; Adult; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Bisulfite; Case-Control Studies; CpG Islands; Deoxyribonucleic acid; Disease Progression; DNA; DNA Methylation; DNA sequencing; Epigenesis, Genetic; Epigenetics; Female; Gene expression; Gene Expression Regulation; Genome-Wide Association Study; Glucose metabolism; Glycolysis; Heterogeneity; HIV; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - pathology; HIV Infections - virology; HIV-1 - isolation & purification; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Latency; Leukocytes (mononuclear); Male; Middle Aged; multidisciplinary; Promoter Regions, Genetic; Science; Science (multidisciplinary); Sustained Virologic Response; Transcription; Viremia; Virus Latency - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02463-0

DNA 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.