ArticleNature communications2021
A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Regulatory NLRs in HSV-1 Infection: Direct Evidence, Comparative Mechanisms and Testable Hypotheses.Pathogens (Basel, Switzerland) · 2026Review
- Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?Pathogens (Basel, Switzerland) · 2025Review
- Mutations in the signal peptide of effector gene Pi04314 contribute to the adaptive evolution of the Phytophthora infestans.BMC ecology and evolution · 2025Article
- Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations.JACC. Basic to translational science · 2024Article
- Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning.eLife · 2024Article
- Innexin hemichannel activation byiScience · 2024Article
- CLPTM1L is a GPI-anchoring pathway component targeted by HCMV.The Journal of cell biology · 2023Article
- Genetic Analysis of Orf Virus (ORFV) Strains Isolated from Goats in China: Insights into Epidemiological Characteristics and Evolutionary Patterns.Virus research · 2023Article
- Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation.Frontiers in immunology · 2023Article
- Glycosylation in SARS-CoV-2 variants: A path to infection and recovery.Biochemical pharmacology · 2022Review
- Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue.International journal of molecular sciences · 2021Article
- The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing.PLoS pathogens · 2021Article
- The Impact of Endoplasmic Reticulum-Associated Protein Modifications, Folding and Degradation on Lung Structure and Function.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress can induce cell surface expression of MHC-like ligands, including MICA, that activate NK cells. Human cytomegalovirus (HCMV) glycoprotein US9 downregulates the activating immune ligand MICA*008 to avoid NK cell activation, but the underlying mechanism remains unclear. Here, we show that the N-terminal signal peptide is the major US9 functional domain targeting MICA*008 to proteasomal degradation. The US9 signal peptide is cleaved with unusually slow kinetics and this transiently retained signal peptide arrests MICA*008 maturation in the endoplasmic reticulum (ER), and indirectly induces its degradation via the ER quality control system and the SEL1L-HRD1 complex. We further identify an accessory, signal peptide-independent US9 mechanism that directly binds MICA*008 and SEL1L. Collectively, we describe a dual-targeting immunoevasin, demonstrating that signal peptides can function as protein-integral effector domains.
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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.