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| Home > Articles > Published articles > Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control |
(Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Universitat de Vic - Universitat Central de Catalunya) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)| Date: | 2020 |
| 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. |
| Grants: | Ministerio de Economía y Competitividad MTM2015-64465-C2-1-R European Commission 681137 Ministerio de Ciencia e Innovación SAF2017-89726-R Ministerio de Educación, Cultura y Deporte FPU15-03698 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Antiviral Agents ; Biomarkers ; CD4-Positive T-Lymphocytes ; DNA Methylation ; Epigenesis, Genetic ; Female ; HIV Infections ; HIV-1 ; Host-Pathogen Interactions ; Humans ; Interferon Regulatory Factors ; Interferons ; Male ; T-Lymphocytes, Helper-Inducer ; Viral Load ; Virus Replication |
| Published in: | PLOS pathogens, Vol. 16 Núm. 8 (june 2020) , p. e1008678, ISSN 1553-7374 |
