ArticlePLoS pathogens2017
The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- SUMOylation-dependent degradation of nucleocapsid is responsible forJournal of virology · 2025Article
- The Function of TER94 of Spodoptera frugiperda 9 Cells When Infected With Invertebrate Iridescent Virus-6.Journal of basic microbiology · 2025Article
- p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- ATPase Valosin-Containing Protein (VCP) Is Involved During the Replication and Egress of Sialodacryoadenitis Virus (SDAV) in Neurons.International journal of molecular sciences · 2024Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- Review
- Optimization of 1,2,4-Triazole-Based p97 Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2023Article
- Valosin-containing protein (VCP/p97) inhibition reduces viral clearance and induces toxicity associated with muscular damage.Cell death & disease · 2022Article
- An eIF3d-dependent switch regulates HCMV replication by remodeling the infected cell translation landscape to mimic chronic ER stress.Cell reports · 2022Article
- 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
- The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- High salt activates p97 to reduce host antiviral immunity by restricting Viperin induction.EMBO reports · 2022Article
- How Viruses Use the VCP/p97 ATPase Molecular Machine.Viruses · 2021Review
- AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors.European journal of medicinal chemistry · 2021Review
- Article
- Valosin-containing protein/p97 plays critical roles in the Japanese encephalitis virus life cycle.Journal of virology · 2021Article
- Viral mediated tethering to SEL1L facilitates ER-associated degradation of IRE1.Journal of virology · 2021Article
- Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion.PLoS pathogens · 2021Article
- White Spot Syndrome Virus Benefits from Endosomal Trafficking, Substantially Facilitated by a Valosin-Containing Protein, To Escape Autophagic Elimination and Propagate in the Crustacean Cherax quadricarinatus.Journal of virology · 2020Article
- The Human Cytomegalovirus Transmembrane Protein pUL50 Induces Loss of VCP/p97 and Is Regulated by a Small Isoform of pUL50.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection.
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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 Socratic graph.