ArticleProceedings of the National Academy of Sciences of the United States of America2021
Bromodomain proteins regulate human cytomegalovirus latency and reactivation allowing epigenetic therapeutic intervention.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Mechanisms and Determinants of CMV Reactivation in Kidney Transplantation.International journal of molecular sciences · 2026Review
- Sensing the storm: how inflammatory signalling drives reactivation of the human cytomegalovirus major immediate-early promoter.The Journal of general virology · 2026Review
- Targeted next-generation sequencing-based pathogens detection in children with severe pneumonia in the pediatric intensive care unit.Frontiers in pediatrics · 2026Article
- Lytic or Latent Phase in Human Cytomegalovirus Infection: An Epigenetic Trigger.International journal of molecular sciences · 2025Review
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Distinct Immunological Landscapes of HCMV-Specific T Cells in Bone Marrow and Peripheral Blood.Pathogens (Basel, Switzerland) · 2025Article
- N6-methyladenosine modification of HCMV IE1 transcript promotes the repressive state of viral genome to achieve latent infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The gut and circulating virome: emerging players in aging and longevity.Frontiers in aging · 2025Review
- An epigenetic human cytomegalovirus infection score predicts viremia risk in seropositive lung transplant recipients.Epigenetics · 2024Article
- Loopy virus or controlled contortionist? 3D regulation of HCMV gene expression by CTCF-driven chromatin interactions.Journal of virology · 2024Review
- Virus-Specific Nanobody-Chimeras Degrade the Human Cytomegalovirus US28 Protein in CD34+ Cells.Pathogens (Basel, Switzerland) · 2024Article
- The Pentamer glycoprotein complex inhibits viral Immediate Early transcription during Human Cytomegalovirus infections.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Viral cis-regulatory elements as sensors of cellular states and environmental cues.Trends in genetics : TIG · 2024Review
- The Triterpenoid MOMORDIN-Ic Inhibits HCMV by Preventing the Initiation of Gene Expression in Eukaryotic Cells.Pathogens (Basel, Switzerland) · 2024Article
- Article
- Host-encoded CTCF regulates human cytomegalovirus latency via chromatin looping.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins.EMBO reports · 2024Article
- A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR.Nucleic acids research · 2024Article
- Relationship between the risk of intestinal mucosal Epstein-Barr virus and/or cytomegalovirus infection and peripheral blood NK cells numbers in patients with ulcerative colitis: a cross-sectional study in Chinese population.Frontiers in microbiology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Reactivation of human cytomegalovirus (HCMV) from latency is a major health consideration for recipients of stem-cell and solid organ transplantations. With over 200,000 transplants taking place globally per annum, virus reactivation can occur in more than 50% of cases leading to loss of grafts as well as serious morbidity and even mortality. Here, we present the most extensive screening to date of epigenetic inhibitors on HCMV latently infected cells and find that histone deacetylase inhibitors (HDACis) and bromodomain inhibitors are broadly effective at inducing virus immediate early gene expression. However, while HDACis, such as myeloid-selective CHR-4487, lead to production of infectious virions, inhibitors of bromodomain (BRD) and extraterminal proteins (I-BETs), including GSK726, restrict full reactivation. Mechanistically, we show that BET proteins (BRDs) are pivotally connected to regulation of HCMV latency and reactivation. Through BRD4 interaction, the transcriptional activator complex P-TEFb (CDK9/CycT1) is sequestered by repressive complexes during HCMV latency. Consequently, I-BETs allow release of P-TEFb and subsequent recruitment to promoters via the superelongation complex (SEC), inducing transcription of HCMV lytic genes encoding immunogenic antigens from otherwise latently infected cells. Surprisingly, this occurs without inducing many viral immunoevasins and, importantly, while also restricting viral DNA replication and full HCMV reactivation. Therefore, this pattern of HCMV transcriptional dysregulation allows effective cytotoxic immune targeting and killing of latently infected cells, thus reducing the latent virus genome load. This approach could be safely used to pre-emptively purge the virus latent reservoir prior to transplantation, thereby reducing HCMV reactivation-related morbidity and mortality.
Indexed as
Identifiers
What OpenQuestion holds
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.