Back to Search
Start Over
Development of 5' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals.
- Source :
-
Clinical Epigenetics . 2/19/2016, Vol. 8, p1-20. 20p. - Publication Year :
- 2016
-
Abstract
- Background: Human immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (5' LTR) restricts HIV-1 reactivation and, together with chromatin conformation, represents an important mechanism of HIV-1 latency maintenance. Here, we explored the new issue of temporal development of DNA methylationinlatentHIV-15' LTR. Results: In the Jurkat CD4+ T cell model of latency, we showed that the stimulation of host cells contributed to de novo DNA methylation of the latent HIV-1 5' LTR sequences. Consecutive stimulations of model CD4+ Tcell line with TNF-α and PMA or with SAHA contributed to the progressive accumulation of 5' LTR DNA methylation. Further, we showed that once established, the highDNAmethylationlevelofthelatent5' LTR in the cell line model was a stable epigenetic mark. Finally, we explored the development of 5' LTR DNA methylation in the latent reservoir of HIV-1-infected individuals who were treated with ART. We detected low levels of 5' LTR DNA methylation in the resting CD4+ Tcellsof the group of patients who were treated for up to 3 years. However, after long-term ART, we observed an accumulation of 5' LTR DNA methylation in the latent reservoir. Importantly, within the latent reservoir of some long-term-treated individuals, we uncovered populations of proviral molecules with a high density of 5' LTR CpG methylation. Conclusions: Our data showed the presence of 5' LTR DNA methylation in the long-term reservoir of HIV-1-infected individuals and implied that the transient stimulation of cells harboring latent proviruses may contribute, at least in part, to the methylation of the HIV-1 promoter. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIV
*HIGHLY active antiretroviral therapy
*DNA methylation
Subjects
Details
- Language :
- English
- ISSN :
- 18687075
- Volume :
- 8
- Database :
- Academic Search Index
- Journal :
- Clinical Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 113186726
- Full Text :
- https://doi.org/10.1186/s13148-016-0185-6