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

Author(s):Show less -

Mantovani, Nathalia ^[1] ; Defelicibus, Alexandre ^[2] ; da Silva, Israel Tojal ^[2] ; Cicero, Maira Ferreira ^[1] ; Santana, Luiz Claudio ^[1] ; Arnold, Rafael ^[1] ; de Castro, Daniela Funayama ^[1] ; Sanz Duro, Rodrigo Lopes ^[1] ; Nishiyama-Jr, Milton Yutaka ; Meirelles Junqueira-de-Azevedo, Inacio Loiola ^[3] ; Maciel da Silva, Bosco Christiano ^[4] ; da Silva Duarte, Alberto Jose ^[4] ; Casseb, Jorge ^[4] ; Tenore, Simone de Barros ^[1] ; Hunter, James ^[1] ; Diaz, Ricardo Sobhie ^[1] ; Vasconcelos Komninakis, Shirley Cavalcante ^[1]

Affiliation

^[1] Fed Univ Sao Paulo UNIFESP, Infect Dis Div, Retrovirol Lab, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo, SP - Brazil

^[2] AC Camargo Canc Ctr, Lab Bioinformat & Computat Biol, Rua Tagua 440, BR-01508010 Sao Paulo, SP - Brazil

^[3] Nishiyama-Jr, Jr., Milton Yutaka, Inst Butantan, Lab Toxinol Aplicada, Ave Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med FMUSP, Lab Invest Med 56 LIM 56, Ave Dr Eneas Carvalho de Aguiar 470, BR-05403000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 NOV 26 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 13/06584-4 - Study of the specific immune response and the identification of HIV-1 epitopes in slow progressor and elite controller individuals infected by the HIV-1
• Grantee: Alberto José da Silva Duarte
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/10396-2 - Multiple interventions to eliminate HIV reservoirs among antiretroviral treated individuals in order to obtain sustained HIV remission without antiretrovirals
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/02652-5 - Epigenetic modification in patients infected with Human Immunodeficiency Virus type 1 (HIV-1)
• Grantee: Shirley Cavalcante Vasconcelos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/09623-3 - Evaluation of the HIV-1 specific cellular immune response, identification of HIV-1 epitopes and role of CD4+CD25+FoxP3+ Regulatory T cells in long-term non progressors (LTNP) and elite controllers (EC) HIV-1 infected individuals
• Grantee: Bosco Christiano Maciel da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctorate