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Increased expression of BCL11B and its recruited chromatin remodeling factors during highly active antiretroviral therapy synergistically represses the transcription of human immunodeficiency virus type 1 and is associated with residual immune activation.
- Source :
-
Archives of virology [Arch Virol] 2020 Feb; Vol. 165 (2), pp. 321-330. Date of Electronic Publication: 2019 Dec 11. - Publication Year :
- 2020
-
Abstract
- Persistence of human immunodeficiency virus 1 (HIV-1) latency and residual immune activation remain major barriers to treatment in patients receiving highly active antiretroviral therapy (HAART). In the present study, we investigated the molecular mechanisms of persistent HIV infection and residual immune activation in HAART-treated patients. We showed that the expression level of B-cell CLL/lymphoma 11B (BCL11B) was significantly increased in CD4 <superscript>+</superscript> T cells from HIV-infected patients undergoing HAART, and this was accompanied by increased expression of BCL11B-associated chromatin modifiers and inflammatory factors in comparison to healthy controls and untreated patients with HIV. In vitro assays showed that BCL11B significantly inhibited HIV-1 long terminal repeat (LTR)-mediated transcription. Knockdown of BCL11B resulted in the activation of HIV latent cells, and dissociation of BCL11B and its related chromatin remodeling factors from the HIV LTR. Our findings suggested that increased expression of BCL11B and its related chromatin modifiers contribute to HIV-1 transcriptional silencing, and alteration of BCL11B levels might lead to abnormal transcription and inflammation.
- Subjects :
- Adult
Antiretroviral Therapy, Highly Active methods
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
Chromatin genetics
Chromatin virology
Chromatin Assembly and Disassembly drug effects
Chromatin Assembly and Disassembly immunology
Female
HIV Infections drug therapy
HIV Infections immunology
HIV Infections virology
HIV Long Terminal Repeat genetics
HIV Long Terminal Repeat immunology
HIV-1 drug effects
HIV-1 immunology
Humans
Male
Transcription, Genetic drug effects
Virus Latency genetics
Virus Latency immunology
Chromatin Assembly and Disassembly genetics
HIV Infections genetics
HIV-1 genetics
Repressor Proteins genetics
Repressor Proteins immunology
Transcription, Genetic immunology
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-8798
- Volume :
- 165
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Archives of virology
- Publication Type :
- Academic Journal
- Accession number :
- 31828511
- Full Text :
- https://doi.org/10.1007/s00705-019-04475-8