Singh, R;
Ramsuran, V;
Naranbhai, V;
Yende-Zuma, N;
Garrett, N;
Mlisana, K;
Dong, KL;
... Ndung’u, T; + view all
(2021)
Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis.
Frontiers in Immunology
, 12
, Article 669241. 10.3389/fimmu.2021.669241.
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Abstract
HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (BST-2), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured in vitro expression levels of BST-2 mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of BST-2 showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating BST-2 levels, where increased BST-2 methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate BST-2 levels using a DNA hypomethylation drug. Our results suggest BST-2 as a factor for potential therapeutic intervention against HIV and other diseases known to involve BST-2.
| Type: | Article |
|---|---|
| Title: | Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2021.669241 |
| Publisher version: | https://doi.org/10.3389/fimmu.2021.669241 |
| Language: | English |
| Additional information: | © 2021 Singh, Ramsuran, Naranbhai, Yende-Zuma, Garrett, Mlisana, Dong, Walker, Abdool Karim, Carrington and Ndung’u. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). |
| Keywords: | BST-2, DNA methylation, HIV-1, epigenetic regulation, expression, Antigens, CD, Blacks, Case-Control Studies, Cells, Cultured, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Female, GPI-Linked Proteins, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Leukocytes, Mononuclear, Longitudinal Studies, Prognosis, South Africa, Viral Load, Virus Replication |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10149491 |
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