Hypoxic microenvironment shapes HIV-1 replication and latency
Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypo...
| Main Authors: | , , , , , , , , , , , , |
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| 格式: | Journal article |
| 语言: | English |
| 出版: |
Nature Research
2020
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| _version_ | 1826256486051872768 |
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| author | Zhuang, X Pedroza-Pacheco, I Nawroth, I Kliszczak, AE Magri, A Paes, W Rubio, CO Yang, H Ashcroft, M Mole, D Balfe, P Borrow, P McKeating, JA |
| author_facet | Zhuang, X Pedroza-Pacheco, I Nawroth, I Kliszczak, AE Magri, A Paes, W Rubio, CO Yang, H Ashcroft, M Mole, D Balfe, P Borrow, P McKeating, JA |
| author_sort | Zhuang, X |
| collection | OXFORD |
| description | Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypoxic environment in vivo. However, the majority of studies on HIV replication and latency are performed under laboratory conditions where HIFs are inactive. We show a role for HIF-2α in restricting HIV transcription via direct binding to the viral promoter. Hypoxia reduced tumor necrosis factor or histone deacetylase inhibitor, Romidepsin, mediated reactivation of HIV and inhibiting HIF signaling-pathways reversed this phenotype. Our data support a model where the low-oxygen environment of the lymph node may suppress HIV replication and promote latency. We identify a mechanism that may contribute to the limited efficacy of latency reversing agents in reactivating HIV and suggest new strategies to control latent HIV-1.
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| first_indexed | 2024-03-06T18:02:59Z |
| format | Journal article |
| id | oxford-uuid:0074d92c-c6d2-489d-a039-0f68bf5ee126 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:02:59Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:0074d92c-c6d2-489d-a039-0f68bf5ee1262022-03-26T08:29:33ZHypoxic microenvironment shapes HIV-1 replication and latencyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0074d92c-c6d2-489d-a039-0f68bf5ee126EnglishSymplectic ElementsNature Research2020Zhuang, XPedroza-Pacheco, INawroth, IKliszczak, AEMagri, APaes, WRubio, COYang, HAshcroft, MMole, DBalfe, PBorrow, PMcKeating, JAViral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypoxic environment in vivo. However, the majority of studies on HIV replication and latency are performed under laboratory conditions where HIFs are inactive. We show a role for HIF-2α in restricting HIV transcription via direct binding to the viral promoter. Hypoxia reduced tumor necrosis factor or histone deacetylase inhibitor, Romidepsin, mediated reactivation of HIV and inhibiting HIF signaling-pathways reversed this phenotype. Our data support a model where the low-oxygen environment of the lymph node may suppress HIV replication and promote latency. We identify a mechanism that may contribute to the limited efficacy of latency reversing agents in reactivating HIV and suggest new strategies to control latent HIV-1. |
| spellingShingle | Zhuang, X Pedroza-Pacheco, I Nawroth, I Kliszczak, AE Magri, A Paes, W Rubio, CO Yang, H Ashcroft, M Mole, D Balfe, P Borrow, P McKeating, JA Hypoxic microenvironment shapes HIV-1 replication and latency |
| title | Hypoxic microenvironment shapes HIV-1 replication and latency |
| title_full | Hypoxic microenvironment shapes HIV-1 replication and latency |
| title_fullStr | Hypoxic microenvironment shapes HIV-1 replication and latency |
| title_full_unstemmed | Hypoxic microenvironment shapes HIV-1 replication and latency |
| title_short | Hypoxic microenvironment shapes HIV-1 replication and latency |
| title_sort | hypoxic microenvironment shapes hiv 1 replication and latency |
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