ArticlePLoS pathogens2014
A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 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
- Nucleotide-dependent conformational changes direct peptide export by the transporter associated with antigen processing.Immunity · 2025Article
- A Structural Atlas of TAP Inhibition by Herpesviruses and Poxviruses.bioRxiv : the preprint server for biology · 2025Article
- A guide to antigen processing and presentation.Nature reviews. 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
- Article
- Fluorescent TAP as a Platform for Virus-Induced Degradation of the Antigenic Peptide Transporter.Cells · 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
- 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
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.
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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.