ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Human cytomegalovirus UL40 signal peptide regulates cell surface expression of the NK cell ligands HLA-E and gpUL18.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 93 citations in OpenAlex.
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Targeting MHC-E as a new strategy for vaccines and immunotherapeutics.Nature reviews. Immunology · 2026Review
- The Expanding Role of HLA-E in Host Defense: A Target for Broadly Applicable Vaccines and Immunotherapies.Cells · 2025Review
- NK and T cell evasion mechanism of human cytomegalovirus.Archives of virology · 2025Review
- Cytomegalovirus Genetic Diversity and Evolution: Insights into Genotypes and Their Role in Viral Pathogenesis.Pathogens (Basel, Switzerland) · 2025Review
- Viral manipulation of the HLA class I antigen processing and presentation pathway.Frontiers in immunology · 2025Review
- Human cytomegalovirus UL18 prevents priming of MHC-E- and MHC-II-restricted CD8Science immunology · 2024Article
- Regulation of the cell surface expression of classical and non-classical MHC proteins by the human cytomegalovirus UL40 and rhesus cytomegalovirus Rh67 proteins.Journal of virology · 2024Article
- Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning.eLife · 2024Article
- Cytomegalovirus, Epstein-Barr Virus, Herpes Simplex Virus, and Varicella Zoster Virus Infection Dynamics in People with Multiple Sclerosis from Northern Italy.Pathogens (Basel, Switzerland) · 2024Article
- Single-cell profiling aligns CD56Frontiers in immunology · 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
- Natural killer cells and their exosomes in viral infections and related therapeutic approaches: where are we?Cell communication and signaling : CCS · 2023Review
- Review
- Activating NKG2C Receptor: Functional Characteristics and Current Strategies in Clinical Applications.Archivum immunologiae et therapiae experimentalis · 2023Review
- Effect of Cytomegalovirus on the Immune System: Implications for Aging and Mental Health.Current topics in behavioral neurosciences · 2023Article
- Life after Cleavage: The Story of a β-Retroviral (MMTV) Signal Peptide-From Murine Lymphoma to Human Breast Cancer.Viruses · 2022Review
- HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection.BMC genomics · 2022Article
- Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome.International journal of molecular sciences · 2022Article
- Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections.Expert opinion on therapeutic targets · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Human CMV (HCMV)-encoded NK cell-evasion functions include an MHC class I homolog (UL18) with high affinity for the leukocyte inhibitory receptor-1 (CD85j, ILT2, or LILRB1) and a signal peptide (SP(UL40)) that acts by upregulating cell surface expression of HLA-E. Detailed characterization of SP(UL40) revealed that the N-terminal 14 aa residues bestowed TAP-independent upregulation of HLA-E, whereas C region sequences delayed processing of SP(UL40) by a signal peptide peptidase-type intramembrane protease. Most significantly, the consensus HLA-E-binding epitope within SP(UL40) was shown to promote cell surface expression of both HLA-E and gpUL18. UL40 was found to possess two transcription start sites, with utilization of the downstream site resulting in translation being initiated within the HLA-E-binding epitope (P2). Remarkably, this truncated SP(UL40) was functional and retained the capacity to upregulate gpUL18 but not HLA-E. Thus, our findings identify an elegant mechanism by which an HCMV signal peptide differentially regulates two distinct NK cell-evasion pathways. Moreover, we describe a natural SP(UL40) mutant that provides a clear example of an HCMV clinical virus with a defect in an NK cell-evasion function and exemplifies issues that confront the virus when adapting to immunogenetic diversity in the host.
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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.