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 

TITLE=Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.669241

DOI=10.3389/fimmu.2021.669241

ISSN=1664-3224

ABSTRACT=<p>HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (<italic>BST-2</italic>), 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 <italic>in vitro</italic> expression levels of <italic>BST-2</italic> mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of <italic>BST-2</italic> 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 <italic>BST-2</italic> levels, where increased <italic>BST-2</italic> methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate <italic>BST-2</italic> levels using a DNA hypomethylation drug. Our results suggest <italic>BST-2</italic> as a factor for potential therapeutic intervention against HIV and other diseases known to involve <italic>BST-2</italic>.</p>