ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Cowpox virus protein CPXV012 eludes CTLs by blocking ATP binding to TAP.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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, 34 citations in OpenAlex.
- Structurally diverse viral inhibitors converge on a shared mechanism to stall the antigen transporter TAP.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Structural Atlas of TAP Inhibition by Herpesviruses and Poxviruses.bioRxiv : the preprint server for biology · 2025Article
- Viral manipulation of the HLA class I antigen processing and presentation pathway.Frontiers in immunology · 2025Review
- Cowpox Viruses: A Zoo Full of Viral Diversity and Lurking Threats.Biomolecules · 2023Review
- Spotlight on TAP and its vital role in antigen presentation and cross-presentation.Molecular immunology · 2022Review
- Viral immune evasins impact antigen presentation by allele-specific trapping of MHC I at the peptide-loading complex.Scientific reports · 2022Article
- Article
- Direct Priming of CD8Journal of virology · 2021Article
- Viruses, cancer and non-self recognition.Open biology · 2021Review
- Article
- Fluorescent TAP as a Platform for Virus-Induced Degradation of the Antigenic Peptide Transporter.Cells · 2019Article
- Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation.PLoS pathogens · 2019Article
- Mutagenic repair of double-stranded DNA breaks in vaccinia virus genomes requires cellular DNA ligase IV activity in the cytosol.The Journal of general virology · 2018Article
- Article
- Cutting Edge: The Aging Immune System Reveals the Biological Impact of Direct Antigen Presentation on CD8 T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus.PloS one · 2017Article
- Exploiting the exploiter: a viral inhibitor stabilizes TAP for cryo-EM.Nature structural & molecular biology · 2016Article
- Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily.Viruses · 2015Review
- Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.PLoS pathogens · 2015Review
- A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.PLoS pathogens · 2014Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
CD8(+) CTLs detect virus-infected cells through recognition of virus-derived peptides presented at the cell surface by MHC class I molecules. The cowpox virus protein CPXV012 deprives the endoplasmic reticulum (ER) lumen of peptides for loading onto newly synthesized MHC class I molecules by inhibiting the transporter associated with Ag processing (TAP). This evasion strategy allows the virus to avoid detection by the immune system. In this article, we show that CPXV012, a 9-kDa type II transmembrane protein, prevents peptide transport by inhibiting ATP binding to TAP. We identified a segment within the ER-luminal domain of CPXV012 that imposes the block in peptide transport by TAP. Biophysical studies show that this domain has a strong affinity for phospholipids that are also abundant in the ER membrane. We discuss these findings in an evolutionary context and show that a frameshift deletion in the CPXV012 gene in an ancestral cowpox virus created the current form of CPXV012 that is capable of inhibiting TAP. In conclusion, our findings indicate that the ER-luminal domain of CPXV012 inserts into the ER membrane, where it interacts with TAP. CPXV012 presumably induces a conformational arrest that precludes ATP binding to TAP and, thus, activity of TAP, thereby preventing the presentation of viral peptides to CTLs.
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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.