ArticleProceedings of the National Academy of Sciences of the United States of America2008
Regulation of protein translation through mRNA structure influences MHC class I loading and T cell recognition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
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- A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes.Nucleic acids research · 2019Article
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- The Critical Role of Genome Maintenance Proteins in Immune Evasion During Gammaherpesvirus Latency.Frontiers in microbiology · 2018Review
- Macavirus latency-associated protein evades immune detection through regulation of protein synthesis in cis depending upon its glycin/glutamate-rich domain.PLoS pathogens · 2017Article
- Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo.Molecular cancer therapeutics · 2016Article
- Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells.PLoS pathogens · 2015Article
- Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- mRNA Structural constraints on EBNA1 synthesis impact on in vivo antigen presentation and early priming of CD8+ T cells.PLoS pathogens · 2014Article
- G-quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation.Nature chemical biology · 2014Article
- A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus.Disease models & mechanisms · 2014Article
- Monitoring peptide processing for MHC class I molecules in the endoplasmic reticulum.Current opinion in immunology · 2014Review
- Therapeutic vaccination against the rhesus lymphocryptovirus EBNA-1 homologue, rhEBNA-1, elicits T cell responses to novel epitopes in rhesus macaques.Journal of virology · 2013Article
- Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses.Current opinion in virology · 2013Review
- Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA conformation: application to disease studies.Nucleic acids research · 2013Article
- Kinetics of antigen expression and epitope presentation during virus infection.PLoS pathogens · 2013Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many viruses avoid immune surveillance during latent infection through reduction in the synthesis of virally encoded proteins. Although antigen presentation critically depends on the level of viral protein synthesis, the precise mechanism used to regulate the generation of antigenic peptide precursors remains elusive. Here, we demonstrate that a purine overloaded virally encoded mRNA lacking secondary structure significantly impacts the efficiency of protein translation and prevents endogenous antigen presentation. Reducing this purine bias through the generation of constructs expressing codon-modified sequences, while maintaining the encoded protein sequence, increased the stem-loop structure of the corresponding mRNA and dramatically enhanced self-synthesis of the viral protein. As a consequence, a higher number of HLA-peptide complexes were detected on the surface of cells expressing this viral protein. Furthermore, these cells were more efficiently recognized by virus-specific T cells compared with those expressing the same antigen expressed by a purine-biased mRNA. These findings delineate a mechanism by which viruses regulate self-synthesis of proteins and offer an effective strategy to evade CD8(+) T cell-mediated immune regulation.
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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.