ArticleJCI insight2020
Epigenetic silencing of CD4 expression in nonpathogenic SIV infection in African green monkeys.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Epigenetic mechanisms of retroviral regulation: a comparative review.Epigenetics & chromatin · 2026Review
- Viremic non-progression in HIV/SIV infection: A tied game between virus and host.Cell reports. Medicine · 2025Review
- Article
- Prolonged experimental CD4Nature communications · 2023Article
- HIV-1 release requires Nef-induced caspase activation.PloS one · 2023Article
- Double-negative T cells are increased in HIV-infected patients under antiretroviral therapy.Medicine · 2022Article
- Epigenetic Reprogramming Leads to Downregulation of CD4 and Functional Changes in African Green Monkey Memory CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Walk on the wild side: SIV infection in African non-human primate hosts-from the field to the laboratory.Frontiers in immunology · 2022Review
- CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Battle for supremacy: nucleic acid interactions between viruses and cells.The Journal of clinical investigation · 2021Review
- Deciphering DNA Methylation in HIV Infection.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
African green monkeys (AGMs) are natural hosts of SIV that postthymically downregulate CD4 to maintain a large population of CD4-CD8aa+ virus-resistant cells with Th functionality, which can result in AGMs becoming apparently cured of SIVagm infection. To understand the mechanisms of this process, we performed genome-wide transcriptional analysis on T cells induced to downregulate CD4 in vitro from AGMs and closely related patas monkeys and T cells that maintain CD4 expression from rhesus macaques. In T cells that downregulated CD4, pathway analysis revealed an atypical regulation of the DNA methylation machinery, which was reversible when pharmacologically targeted with 5-aza-2 deoxycytidine. This signature was driven largely by the dioxygenase TET3, which became downregulated with loss of CD4 expression. CpG motifs within the AGM CD4 promoter region became methylated during CD4 downregulation in vitro and were stably imprinted in AGM CD4-CD8aa+ T cells sorted directly ex vivo. These results suggest that AGMs use epigenetic mechanisms to durably silence the CD4 gene. Manipulation of these mechanisms could provide avenues for modulating SIV and HIV-1 entry receptor expression in hosts that become progressively infected with SIV, which could lead to novel therapeutic interventions aimed to reduce HIV viremia in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.