Hypoxic microenvironment shapes HIV-1 replication and latency
| Autor: | Persephone Borrow, Margaret Ashcroft, Jane A. McKeating, Xiaodong Zhuang, Andrea Magri, Anna E. Kliszczak, David R. Mole, Hongbing Yang, Peter Balfe, Claudia Orbegozo Rubio, Wayne Paes, Isabel Nawroth, Isabela Pedroza-Pacheco |
|---|---|
| Přispěvatelé: | Paes, Wayne [0000-0002-0529-2765], Ashcroft, Margaret [0000-0002-0066-3707], Balfe, Peter [0000-0002-6246-0876], Borrow, Persephone [0000-0002-3877-9780], McKeating, Jane A. [0000-0002-7229-5886], Apollo - University of Cambridge Repository, McKeating, Jane A [0000-0002-7229-5886] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.drug_class Lymphoid Tissue 96 Medicine (miscellaneous) Biology Virus-host interactions Real-Time Polymerase Chain Reaction Virus Replication General Biochemistry Genetics and Molecular Biology Article Romidepsin 38 Viral Transcription 03 medical and health sciences 13/1 0302 clinical medicine Transcription (biology) 631/326/596/2557 medicine Basic Helix-Loop-Helix Transcription Factors Humans Hypoxia Promoter Regions Genetic lcsh:QH301-705.5 64 82 Histone deacetylase inhibitor virus diseases 631/250/254 Flow Cytometry Phenotype 3. Good health Oxygen tension Virus Latency Oxygen 030104 developmental biology Viral replication Hypoxia-inducible factors lcsh:Biology (General) Cellular Microenvironment 030220 oncology & carcinogenesis Cancer research HIV-1 Tumor necrosis factor alpha Virus Activation General Agricultural and Biological Sciences Infection medicine.drug |
| Zdroj: | Communications Biology Communications Biology, Vol 3, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2399-3642 |
| Popis: | 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. Zhuang et al. investigate how low oxygen levels affect HIV-1 replication in cell culture models. They find that the hypoxia-induced transcription factor HIF-2α represses HIV transcription and that low oxygen reduces the reactivation of latent HIV, suggesting that the hypoxic environment in the lymph node may influence HIV replication and latency. |
| Databáze: | OpenAIRE |
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