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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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