ArticlePloS one2017
Epigenetically repressing human cytomegalovirus lytic infection and reactivation from latency in THP-1 model by targeting H3K9 and H3K27 histone demethylases.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- DNA methylation and gene expression signatures for common childhood infections.Clinical epigenetics · 2026Article
- Viral and host network analysis of the human cytomegalovirus transcriptome in latency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modeling and Remodeling the Cell: How Digital Twins and HCMV Can Elucidate the Complex Interactions of Viral Latency, Epigenetic Regulation, and Immune Responses.Current clinical microbiology reports · 2023Article
- Review
- Epigenetic Regulation by Polycomb Complexes from Drosophila to Human and Its Relation to Communicable Disease Pathogenesis.International journal of molecular sciences · 2022Review
- Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP.International journal of molecular sciences · 2022Article
- Review
- Epigenetic reprogramming of host and viral genes by Human Cytomegalovirus infection in Kasumi-3 myeloid progenitor cells at early times post-infection.Journal of virology · 2021Article
- Bromodomain proteins regulate human cytomegalovirus latency and reactivation allowing epigenetic therapeutic intervention.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- New Insights Into the Molecular Mechanisms and Immune Control of Cytomegalovirus Reactivation.Transplantation · 2020Review
- Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response.Frontiers in cellular and infection microbiology · 2020Review
- JMJD3 in the regulation of human diseases.Protein & cell · 2019Review
- Cell Line Models for Human Cytomegalovirus Latency Faithfully Mimic Viral Entry by Macropinocytosis and Endocytosis.Journal of virology · 2019Article
- A clinically relevant murine model unmasks a "two-hit" mechanism for reactivation and dissemination of cytomegalovirus after kidney transplant.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Control of viral infections by epigenetic-targeted therapy.Clinical epigenetics · 2019Review
- Article
- Epigenetic Priming in Immunodeficiencies.Frontiers in cell and developmental biology · 2019Review
- Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation.Viruses · 2018Review
- Article
- Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics.Vaccines · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human Cytomegalovirus (hCMV) infects a broad range of the population and establishes life-long latency in the infected individuals. Periodically the latently infected virus can reactivate and becomes a significant cause of morbidity and mortality in immunocompromised individuals. In latent infection, the viral genome is suppressed in a heterochromatic state and viral gene transcription is silenced. Upon reactivation, the repressive chromatin is remodeled to an active form, allowing viral lytic gene transcription, initiated by the expression of viral Immediate Early (IE) genes. During this process, a number of histone modification enzymes, including histone demethylases (HDMs), play important roles in driving IE expression, but the mechanisms involved are not fully understood. To get a better understanding of these mechanisms, we focused on two HDMs, KDM4 and KDM6, which reverse the repressive histone H3-lysine 9 and lysine 27 methylation, respectively. Our studies show that in lytic infection, both demethylases are important in the activation of viral IE gene expression. Simultaneous disruption of both via genetic or chemical methods leads to severely impaired viral IE gene expression and viral replication. Additionally, in an experimental latency-reactivation model in THP-1 cells, the KDM6 family member JMJD3 is induced upon viral reactivation and its knockdown resulted in reduced IE gene transcription. These findings suggest pharmacological inhibition of these HDMs may potentially block hCMV lytic infection and reactivation, and control the viral infection associated diseases, which are of significant unmet medical needs.
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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.