ArticleProceedings of the National Academy of Sciences of the United States of America2020
HCMV-induced signaling through gB-EGFR engagement is required for viral trafficking and nuclear translocation in primary human monocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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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.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Cytomegalovirus latency-the sum of subtleties.Journal of virology · 2025Review
- Herpesvirus initiation of dementias and autoimmune diseases.Journal of neurovirology · 2025Review
- Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34Antiviral research · 2025Article
- RAF1 promotes successful human cytomegalovirus replication and is regulated by AMPK-mediated phosphorylation during infection.Journal of virology · 2025Article
- Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.Science signaling · 2024Article
- Article
- Distinct early role of PTEN regulation during HCMV infection of monocytes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.Journal of virology · 2024Article
- SNX27:Retromer:ESCPE-1-mediated early endosomal tubulation impacts cytomegalovirus replication.Frontiers in cellular and infection microbiology · 2024Article
- Role of Virus-Induced EGFR Trafficking in Proviral Functions.Biomolecules · 2023Review
- The potential of swine pseudorabies virus attenuated vaccine for oncolytic therapy against malignant tumors.Journal of experimental & clinical cancer research : CR · 2023Article
- Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins.bioRxiv : the preprint server for biology · 2023Article
- Restructured membrane contacts rewire organelles for human cytomegalovirus infection.Nature communications · 2022Article
- Human Cytomegalovirus Manipulates Syntaxin 6 for Successful Trafficking and Subsequent Infection of Monocytes.Journal of virology · 2022Article
- Review
- Modulation of host cell signaling during cytomegalovirus latency and reactivation.Virology journal · 2021Review
- STING facilitates nuclear import of herpesvirus genome during infection.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections.Frontiers in cellular and infection microbiology · 2021Review
- Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells.Frontiers in microbiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Previous analysis of postentry events revealed that human cytomegalovirus (HCMV) displays a unique, extended nuclear translocation pattern in monocytes. We determined that c-Src signaling through pentamer engagement of integrins is required upon HCMV entry to avoid sorting of the virus into late endosomes and subsequent degradation. To follow up on this previous study, we designed experiments to investigate how HCMV-induced signaling through the other major axis-the epidermal growth factor receptor (EGFR) kinase-regulates viral postentry events. Here we show that HCMV induces chronic and functional EGFR signaling that is distinct to the virus as compared to the natural EGFR ligand: EGF. This chronic EGFR kinase activity in infected monocytes is required for the proper subcellular localization of the viral particle during trafficking events, as well as for promoting translocation of viral DNA into the host nucleus. Our data indicate that HCMV glycoprotein B (gB) binds to EGFR at the monocyte surface, the virus and EGFR are internalized together, and gB remains bound to EGFR throughout viral postentry events until de-envelopment to promote the chronic EGFR kinase activity required for viral trafficking and nuclear translocation. These data highlight how initial EGFR signaling via viral binding is necessary for entry, but not sufficient to promote each viral trafficking event. HCMV appears to manipulate the EGFR kinase postentry, via gB-EGFR interaction, to be active at the critical points throughout the trafficking process that leads to nuclear translocation and productive infection of peripheral blood monocytes.
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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.