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

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 mono...

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Autores principales:	Nathalia Mantovani, Alexandre Defelicibus, Israel Tojal da Silva, Maira Ferreira Cicero, Luiz Claudio Santana, Rafael Arnold, Daniela Funayama de Castro, Rodrigo Lopes Sanz Duro, Milton Yutaka Nishiyama-Jr, Inácio Loiola Meirelles Junqueira-de-Azevedo, Bosco Christiano Maciel da Silva, Alberto José da Silva Duarte, Jorge Casseb, Simone de Barros Tenore, James Hunter, Ricardo Sobhie Diaz, Shirley Cavalcante Vasconcelos Komninakis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/548fdb99304d4d5f93a2e1b1a3235236
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spelling	oai:doaj.org-article:548fdb99304d4d5f93a2e1b1a32352362021-11-28T12:20:16ZLatency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response10.1038/s41598-021-02463-02045-2322https://doaj.org/article/548fdb99304d4d5f93a2e1b1a32352362021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02463-0https://doaj.org/toc/2045-2322Abstract 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.Nathalia MantovaniAlexandre DefelicibusIsrael Tojal da SilvaMaira Ferreira CiceroLuiz Claudio SantanaRafael ArnoldDaniela Funayama de CastroRodrigo Lopes Sanz DuroMilton Yutaka Nishiyama-JrInácio Loiola Meirelles Junqueira-de-AzevedoBosco Christiano Maciel da SilvaAlberto José da Silva DuarteJorge CassebSimone de Barros TenoreJames HunterRicardo Sobhie DiazShirley Cavalcante Vasconcelos KomninakisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathalia Mantovani Alexandre Defelicibus Israel Tojal da Silva Maira Ferreira Cicero Luiz Claudio Santana Rafael Arnold Daniela Funayama de Castro Rodrigo Lopes Sanz Duro Milton Yutaka Nishiyama-Jr Inácio Loiola Meirelles Junqueira-de-Azevedo Bosco Christiano Maciel da Silva Alberto José da Silva Duarte Jorge Casseb Simone de Barros Tenore James Hunter Ricardo Sobhie Diaz Shirley Cavalcante Vasconcelos Komninakis Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
description	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.
format	article
author	Nathalia Mantovani Alexandre Defelicibus Israel Tojal da Silva Maira Ferreira Cicero Luiz Claudio Santana Rafael Arnold Daniela Funayama de Castro Rodrigo Lopes Sanz Duro Milton Yutaka Nishiyama-Jr Inácio Loiola Meirelles Junqueira-de-Azevedo Bosco Christiano Maciel da Silva Alberto José da Silva Duarte Jorge Casseb Simone de Barros Tenore James Hunter Ricardo Sobhie Diaz Shirley Cavalcante Vasconcelos Komninakis
author_facet	Nathalia Mantovani Alexandre Defelicibus Israel Tojal da Silva Maira Ferreira Cicero Luiz Claudio Santana Rafael Arnold Daniela Funayama de Castro Rodrigo Lopes Sanz Duro Milton Yutaka Nishiyama-Jr Inácio Loiola Meirelles Junqueira-de-Azevedo Bosco Christiano Maciel da Silva Alberto José da Silva Duarte Jorge Casseb Simone de Barros Tenore James Hunter Ricardo Sobhie Diaz Shirley Cavalcante Vasconcelos Komninakis
author_sort	Nathalia Mantovani
title	Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
title_short	Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
title_full	Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
title_fullStr	Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
title_full_unstemmed	Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
title_sort	latency-associated dna methylation patterns among hiv-1 infected individuals with distinct disease progression courses or antiretroviral virologic response
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/548fdb99304d4d5f93a2e1b1a3235236
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Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response

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