ArticlePLoS pathogens2015
Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Human cytomegalovirus infection and coronary heart disease: a systematic review.Virology journal · 2018Pooled it
- CRISPR-Cas9-mediated knock-in of cytomegalovirus US2 provides an alternative strategy for generating hypoimmunogenic hiPSC lines.Scientific reports · 2026Article
- HCMV-pUS2 Disrupts cGAS-STING Signaling through LMAN2L Degradation.PLoS pathogens · 2026Article
- Auguries of adaptivity: LES γδ TCR ligand recognition revisited.Trends in immunology · 2026Review
- The race between viral immune evasion and the MHC class I antigen processing pathway.FEMS microbiology reviews · 2026Review
- The immune response to human cytomegalovirus: impact of age, co-morbidities and the significance of anti-viral activity assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Virion proteomics of genetically intact HCMV reveals a regulator of envelope glycoprotein composition that protects against humoral immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The GATE glycoprotein complex enhances human cytomegalovirus entry in endothelial cells.Nature microbiology · 2025Article
- Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?Pathogens (Basel, Switzerland) · 2025Review
- Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor.The Journal of biological chemistry · 2025Article
- Deletion of the Human Cytomegalovirus US2 to US11 Gene Family Members Impairs the Type-I Interferon Response.Viruses · 2025Article
- A Primer on Proteomic Characterization of Intercellular Communication in a Virus Microenvironment.Molecular & cellular proteomics : MCP · 2025Review
- HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L.The Journal of general virology · 2024Article
- Host Subcellular Organelles: Targets of Viral Manipulation.International journal of molecular sciences · 2024Review
- CD81 suppresses NF-κB signaling and is downregulated in hepatitis C virus expressing cells.Frontiers in cellular and infection microbiology · 2024Article
- HCMV-secreted glycoprotein gpUL4 inhibits TRAIL-mediated apoptosis and NK cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ubiquitin-Dependent and Independent Proteasomal Degradation in Host-Pathogen Interactions.Molecules (Basel, Switzerland) · 2023Review
- Review
- Deletion of the non-adjacent genesFrontiers in immunology · 2023Article
- Viruses Hijack ERAD to Regulate Their Replication and Propagation.International journal of molecular sciences · 2022Review
2 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
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed US2 was unique in downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ and thrombomodulin. US2 recruited the cellular E3 ligase TRC8 to direct the proteasomal degradation of all its targets, reminiscent of its degradation of MHC-I. Whereas integrin α-chains were selectively degraded, their integrin β1 binding partner accumulated in the ER. Consequently integrin signaling, cell adhesion and migration were strongly suppressed. US2 was necessary and sufficient for degradation of the majority of its substrates, but remarkably, the HCMV NK cell evasion function UL141 requisitioned US2 to enhance downregulation of the NK cell ligand CD112. UL141 retained CD112 in the ER from where US2 promoted its TRC8-dependent retrotranslocation and degradation. These findings redefine US2 as a multifunctional degradation hub which, through recruitment of the cellular E3 ligase TRC8, modulates diverse immune pathways involved in antigen presentation, NK cell activation, migration and coagulation; and highlight US2's impact on HCMV pathogenesis.
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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.