ArticlePLoS pathogens2016
Opposing Regulation of the EGF Receptor: A Molecular Switch Controlling Cytomegalovirus Latency and Replication.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Infection with human cytomegalovirus, Epstein-Barr virus, and high-risk types 16 and 18 of human papillomavirus in EGFR-mutated lung adenocarcinoma.Croatian medical journal · 2023Pooled it
- Mechanisms and Determinants of CMV Reactivation in Kidney Transplantation.International journal of molecular sciences · 2026Review
- DNA damage responses in HCMV infection: emerging mechanisms and outstanding questions.Journal of virology · 2026Review
- Reactivation and Management of Endogenous Latent Herpesviruses in the Spaceflight Environment.Current microbiology · 2026Review
- Cytomegalovirus latency-the sum of subtleties.Journal of virology · 2025Review
- Herpesvirus initiation of dementias and autoimmune diseases.Journal of neurovirology · 2025Review
- 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
- Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34Antiviral research · 2025Article
- HCMV strain- and cell type-specific alterations in membrane contact sites point to the convergent regulation of organelle remodeling.Journal of virology · 2024Article
- Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.Science signaling · 2024Article
- Host-encoded CTCF regulates human cytomegalovirus latency via chromatin looping.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Human cytomegalovirus and neonatal infection.Current research in microbial sciences · 2024Review
- Role of Virus-Induced EGFR Trafficking in Proviral Functions.Biomolecules · 2023Review
- Stabilization of the human cytomegalovirus UL136p33 reactivation determinant overcomes the requirement for UL135 for replication in hematopoietic cells.Journal of virology · 2023Article
- Review
- Liver X Receptor-Inducible Host E3 Ligase IDOL Targets a Human Cytomegalovirus Reactivation Determinant.Journal of virology · 2023Article
- Human cytomegalovirus UL138 interaction with USP1 activates STAT1 in infection.PLoS pathogens · 2023Article
- Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins.bioRxiv : the preprint server for biology · 2023Article
- Human Cytomegalovirus UL138 Interaction with USP1 Activates STAT1 in infection.bioRxiv : the preprint server for biology · 2023Article
- Hematopoietic stem cells and betaherpesvirus latency.Frontiers in cellular and infection microbiology · 2023Review
15 more citing papers are in PubMed but not listed here.
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 2 institutions in 1 country.
Funding
Abstract
Herpesviruses persist indefinitely in their host through complex and poorly defined interactions that mediate latent, chronic or productive states of infection. Human cytomegalovirus (CMV or HCMV), a ubiquitous β-herpesvirus, coordinates the expression of two viral genes, UL135 and UL138, which have opposing roles in regulating viral replication. UL135 promotes reactivation from latency and virus replication, in part, by overcoming replication-suppressive effects of UL138. The mechanism by which UL135 and UL138 oppose one another is not known. We identified viral and host proteins interacting with UL138 protein (pUL138) to begin to define the mechanisms by which pUL135 and pUL138 function. We show that pUL135 and pUL138 regulate the viral cycle by targeting that same receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR). EGFR is a major homeostatic regulator involved in cellular proliferation, differentiation, and survival, making it an ideal target for viral manipulation during infection. pUL135 promotes internalization and turnover of EGFR from the cell surface, whereas pUL138 preserves surface expression and activation of EGFR. We show that activated EGFR is sequestered within the infection-induced, juxtanuclear viral assembly compartment and is unresponsive to stress. Intriguingly, these findings suggest that CMV insulates active EGFR in the cell and that pUL135 and pUL138 function to fine-tune EGFR levels at the cell surface to allow the infected cell to respond to extracellular cues. Consistent with the role of pUL135 in promoting replication, inhibition of EGFR or the downstream phosphoinositide 3-kinase (PI3K) favors reactivation from latency and replication. We propose a model whereby pUL135 and pUL138 together with EGFR comprise a molecular switch that regulates states of latency and replication in HCMV infection by regulating EGFR trafficking to fine tune EGFR signaling.
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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.