ArticleThe Journal of biological chemistry2019
Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Mechanisms and Determinants of CMV Reactivation in Kidney Transplantation.International journal of molecular sciences · 2026Review
- Human Cytomegalovirus UL4 is Required for Viral Reactivation via Cellular Reprogramming in Latently Infected CD34+ Progenitor Cells and Humanized Mice.bioRxiv : the preprint server for biology · 2026Article
- Sensing the storm: how inflammatory signalling drives reactivation of the human cytomegalovirus major immediate-early promoter.The Journal of general virology · 2026Review
- The Triterpenoid MOMORDIN-Ic Inhibits HCMV by Preventing the Initiation of Gene Expression in Eukaryotic Cells.Pathogens (Basel, Switzerland) · 2024Article
- Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8Science advances · 2023Article
- The Human Cytomegalovirus β2.7 Long Non-Coding RNA Prevents Induction of Reactive Oxygen Species to Maintain Viral Gene Silencing during Latency.International journal of molecular sciences · 2022Article
- Review
- Review
- Modulation of host cell signaling during cytomegalovirus latency and reactivation.Virology journal · 2021Review
- Review
- 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
- CMV-encoded GPCR pUL33 activates CREB and facilitates its recruitment to the MIE locus for efficient viral reactivation.Journal of cell science · 2021Article
- CD34Journal of virology · 2021Article
- Latent Cytomegalovirus-Driven Recruitment of Activated CD4+ T Cells Promotes Virus Reactivation.Frontiers in immunology · 2021Article
- Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- FOXO transcription factors activate alternative major immediate early promoters to induce human cytomegalovirus reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Role of the Human CytomegalovirusViruses · 2020Review
- Human cytomegalovirus major immediate early transcripts arise predominantly from the canonical major immediate early promoter in reactivating progenitor-derived dendritic cells.The Journal of general virology · 2020Article
- New Insights Into the Molecular Mechanisms and Immune Control of Cytomegalovirus Reactivation.Transplantation · 2020Review
- Cell signaling and cytomegalovirus reactivation: what do Src family kinases have to do with it?Biochemical Society transactions · 2020Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Human cytomegalovirus (HCMV) latency and reactivation rely on a complex interplay between cellular differentiation, cell signaling pathways, and viral gene functions. HCMV reactivation in dendritic cells (DCs) is triggered by IL-6 and extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase signaling. However, activation of the same pathway fails to reactivate HCMV in other myeloid cell types, despite this signaling axis being active in those cells. We hypothesized that IL-6-induced ERK activation initiates the changes in chromatin structure required for viral reactivation but that a concomitant signal is necessary to complete the changes in chromatin structure required for gene expression to occur. Using a differential phosphoproteomics approach in cells that do or do not support IL-6-induced viral reactivation, we identified the concomitant activation of an Src family kinase (SFK), hematopoietic cell kinase (HCK), specifically in DCs in response to IL-6. Pharmacological and genetic inhibition of HCK activity indicated that HCK is required for HCMV reactivation. Furthermore, the HCK/SFK activity was linked to recruitment of the monocytic leukemia zinc finger protein (MOZ) histone acetyltransferase to the viral promoter, which promoted histone acetylation after ERK-mediated histone phosphorylation. Importantly, pharmacological and genetic inhibition of MOZ activity prevented reactivation. These results provide an explanation for the selective activation of viral gene expression in DCs by IL-6, dependent on concomitant SFK and ERK signaling. They also reveal a previously unreported role for SFK activity in the regulation of chromatin structure at promoters in eukaryotic cells via MOZ histone acetyltransferase activity.
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