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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.669241/full |
| id |
doaj-c54a37bd881a413e9e5f2f105c2529ed |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Ravesh Singh Ravesh Singh Ravesh Singh Veron Ramsuran Veron Ramsuran Veron Ramsuran Veron Ramsuran Vivek Naranbhai Vivek Naranbhai Vivek Naranbhai Nonhlanhla Yende-Zuma Nigel Garrett Koleka Mlisana Krista L. Dong Bruce D. Walker Bruce D. Walker Bruce D. Walker Salim S. Abdool Karim Mary Carrington Mary Carrington Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u |
| spellingShingle |
Ravesh Singh Ravesh Singh Ravesh Singh Veron Ramsuran Veron Ramsuran Veron Ramsuran Veron Ramsuran Vivek Naranbhai Vivek Naranbhai Vivek Naranbhai Nonhlanhla Yende-Zuma Nigel Garrett Koleka Mlisana Krista L. Dong Bruce D. Walker Bruce D. Walker Bruce D. Walker Salim S. Abdool Karim Mary Carrington Mary Carrington Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis Frontiers in Immunology BST-2 HIV-1 DNA methylation epigenetic regulation expression |
| author_facet |
Ravesh Singh Ravesh Singh Ravesh Singh Veron Ramsuran Veron Ramsuran Veron Ramsuran Veron Ramsuran Vivek Naranbhai Vivek Naranbhai Vivek Naranbhai Nonhlanhla Yende-Zuma Nigel Garrett Koleka Mlisana Krista L. Dong Bruce D. Walker Bruce D. Walker Bruce D. Walker Salim S. Abdool Karim Mary Carrington Mary Carrington Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u Thumbi Ndung’u |
| author_sort |
Ravesh Singh |
| title |
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_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_sort |
epigenetic regulation of bst-2 expression levels and the effect on hiv-1 pathogenesis |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2021-05-01 |
| 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. |
| topic |
BST-2 HIV-1 DNA methylation epigenetic regulation expression |
| url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.669241/full |
| work_keys_str_mv |
AT raveshsingh epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT raveshsingh epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT raveshsingh epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT veronramsuran epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT veronramsuran epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT veronramsuran epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT veronramsuran epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT viveknaranbhai epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT viveknaranbhai epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT viveknaranbhai epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT nonhlanhlayendezuma epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT nigelgarrett epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT kolekamlisana epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT kristaldong epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT brucedwalker epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT brucedwalker epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT brucedwalker epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT salimsabdoolkarim epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT marycarrington epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT marycarrington epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT thumbindungu epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT thumbindungu epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT thumbindungu epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT thumbindungu epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis AT thumbindungu epigeneticregulationofbst2expressionlevelsandtheeffectonhiv1pathogenesis |
| _version_ |
1721475634808487936 |
| spelling |
doaj-c54a37bd881a413e9e5f2f105c2529ed2021-05-05T04:32:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.669241669241Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 PathogenesisRavesh Singh0Ravesh Singh1Ravesh Singh2Veron Ramsuran3Veron Ramsuran4Veron Ramsuran5Veron Ramsuran6Vivek Naranbhai7Vivek Naranbhai8Vivek Naranbhai9Nonhlanhla Yende-Zuma10Nigel Garrett11Koleka Mlisana12Krista L. Dong13Bruce D. Walker14Bruce D. Walker15Bruce D. Walker16Salim S. Abdool Karim17Mary Carrington18Mary Carrington19Thumbi Ndung’u20Thumbi Ndung’u21Thumbi Ndung’u22Thumbi Ndung’u23Thumbi Ndung’u24HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute (AHRI), Durban, South AfricaDepartment of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban, South AfricaSchool of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South AfricaThe Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, United StatesBasic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, Bethesda, MD, United StatesCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South AfricaThe Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, United StatesBasic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, Bethesda, MD, United StatesCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South AfricaDepartment of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban, South AfricaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute (AHRI), Durban, South AfricaThe Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, United StatesCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South AfricaThe Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, United StatesBasic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, Bethesda, MD, United StatesHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute (AHRI), Durban, South AfricaThe Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, United StatesMax Planck Institute for Infection Biology, Chariteplatz, Berlin, GermanyDivision of Infection and Immunity, University College London, London, United KingdomHIV-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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.669241/fullBST-2HIV-1DNA methylationepigenetic regulationexpression |