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Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis
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 prote...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131512/ https://www.ncbi.nlm.nih.gov/pubmed/34025670 http://dx.doi.org/10.3389/fimmu.2021.669241 |
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author | Singh, Ravesh Ramsuran, Veron Naranbhai, Vivek Yende-Zuma, Nonhlanhla Garrett, Nigel Mlisana, Koleka Dong, Krista L. Walker, Bruce D. Abdool Karim, Salim S. Carrington, Mary Ndung’u, Thumbi |
author_facet | Singh, Ravesh Ramsuran, Veron Naranbhai, Vivek Yende-Zuma, Nonhlanhla Garrett, Nigel Mlisana, Koleka Dong, Krista L. Walker, Bruce D. Abdool Karim, Salim S. Carrington, Mary Ndung’u, Thumbi |
author_sort | Singh, Ravesh |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8131512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81315122021-05-20 Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis Singh, Ravesh Ramsuran, Veron Naranbhai, Vivek Yende-Zuma, Nonhlanhla Garrett, Nigel Mlisana, Koleka Dong, Krista L. Walker, Bruce D. Abdool Karim, Salim S. Carrington, Mary Ndung’u, Thumbi Front Immunol Immunology 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. Frontiers Media S.A. 2021-05-05 /pmc/articles/PMC8131512/ /pubmed/34025670 http://dx.doi.org/10.3389/fimmu.2021.669241 Text en Copyright © 2021 Singh, Ramsuran, Naranbhai, Yende-Zuma, Garrett, Mlisana, Dong, Walker, Abdool Karim, Carrington and Ndung’u https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Singh, Ravesh Ramsuran, Veron Naranbhai, Vivek Yende-Zuma, Nonhlanhla Garrett, Nigel Mlisana, Koleka Dong, Krista L. Walker, Bruce D. Abdool Karim, Salim S. Carrington, Mary Ndung’u, Thumbi Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
title | Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
title_full | Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
title_fullStr | Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
title_full_unstemmed | Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
title_short | Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis |
title_sort | epigenetic regulation of bst-2 expression levels and the effect on hiv-1 pathogenesis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131512/ https://www.ncbi.nlm.nih.gov/pubmed/34025670 http://dx.doi.org/10.3389/fimmu.2021.669241 |
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