Universidad Peruana Cayetano Heredia

Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control

Mostrar el registro sencillo del ítem

dc.contributor.author Oriol-Tordera, B.
dc.contributor.author Berdasco, M.
dc.contributor.author Llano, A.
dc.contributor.author Mothe, B.
dc.contributor.author Gálvez, C.
dc.contributor.author Martinez-Picado, J.
dc.contributor.author Carrillo, J.
dc.contributor.author Blanco, J.
dc.contributor.author Duran-Castells, C.
dc.contributor.author Ganoza, Carmela
dc.contributor.author Sanchez, J.
dc.contributor.author Clotet, B.
dc.contributor.author Calle, M.L.
dc.contributor.author Sánchez-Pla, A.
dc.contributor.author Esteller, M.
dc.contributor.author Brander, C.
dc.contributor.author Ruiz-Riol, M.
dc.date.accessioned 2020-12-14T16:10:02Z
dc.date.available 2020-12-14T16:10:02Z
dc.date.issued 2020
dc.identifier.uri https://hdl.handle.net/20.500.12866/8753
dc.description.abstract GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS Pathogens
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject DNA methylation en_US
dc.subject HIV-1 en_US
dc.subject T cells en_US
dc.subject Epigenetics en_US
dc.subject Viral load en_US
dc.subject Immune response en_US
dc.subject Antiviral immune response en_US
dc.subject Viral gene expression en_US
dc.title Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/JOURNAL.PPAT.1008678
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.09
dc.relation.issn 1553-7374


Ficheros en el ítem

Ficheros Tamaño Formato Ver

No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

info:eu-repo/semantics/restrictedAccess Excepto si se señala otra cosa, la licencia del ítem se describe como info:eu-repo/semantics/restrictedAccess

Buscar en el Repositorio


Listar

Panel de Control

Estadísticas