TY - JOUR
T1 - Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis
AU - Singh, Ravesh
AU - Ramsuran, Veron
AU - Naranbhai, Vivek
AU - Yende-Zuma, Nonhlanhla
AU - Garrett, Nigel
AU - Mlisana, Koleka
AU - Dong, Krista L.
AU - Walker, Bruce D.
AU - Abdool Karim, Salim S.
AU - Carrington, Mary
AU - Ndung’u, Thumbi
N1 - Funding Information:
This study was supported by the South African Department of Science and Innovation/National Research Foundation Research Chairs Initiative (SARChI) grant to TN, a grant from the Swiss South Africa Joint Research Programme (SSAJRP) to TN. Partial funding for this work was received from the Gates Foundation, the International AIDS Vaccine Initiative (IAVI) (UKZNRSA1001) and Gilead Sciences (grant ID #00406). RS was supported by the Columbia University-Southern African Fogarty AIDS International Discovery and Research Program (AITRP) through the Fogarty International Center, National Institutes of Health (grant # D43TW000231). VR is a FLAIR Research Fellow (FLAIR Fellowship programme is partnership between the African Academy of Sciences and the Royal Society that is funded by the UK Government as part of the Global Challenge Research Fund [GCRF]), and was supported by the South African Medical Research Council (SAMRC) with funds from the Department of Science and Technology. This work was also supported in part through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant # 107752/Z/15/Z], the Africa Health Research Institute (AHRI) Wellcome Strategic Core award [grant # 201433/Z16/Z] and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research.
Publisher Copyright:
© Copyright © 2021 Singh, Ramsuran, Naranbhai, Yende-Zuma, Garrett, Mlisana, Dong, Walker, Abdool Karim, Carrington and Ndung’u.
PY - 2021/5/5
Y1 - 2021/5/5
N2 - 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.
AB - 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.
KW - BST-2
KW - DNA methylation
KW - epigenetic regulation
KW - expression
KW - HIV-1
UR - http://www.scopus.com/inward/record.url?scp=85106033677&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.669241
DO - 10.3389/fimmu.2021.669241
M3 - Article
C2 - 34025670
AN - SCOPUS:85106033677
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 669241
ER -
