Self-Inhibition of Synthesis and Antigen Presentation by Epstein-Barr Virus-Encoded EBNA1

• Published in: Science (American Association for the Advancement of Science) 2003-09, Vol.301 (5638), p.1371-1374
• Main Authors: Yin, Yili, Manoury, Bénédicte, Fåhraeus, Robin
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Antibodies; Antigen Presentation; Antigen-antibody reactions; B lymphocytes; Biological and medical sciences; Cells; Cellular immunity; Chemical properties; Coding; Cysteine Endopeptidases - metabolism; Delta cells; eIF-2 Kinase - metabolism; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens - chemistry; Epstein-Barr Virus Nuclear Antigens - genetics; Epstein-Barr Virus Nuclear Antigens - immunology; Epstein-Barr Virus Nuclear Antigens - metabolism; Fundamental and applied biological sciences. Psychology; Genetics; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - physiology; Histocompatibility Antigens Class I - immunology; Humans; Inhibition; Messenger RNA; MHC antibodies; Microbiology; Multienzyme Complexes - metabolism; Observation; Ova; Peptides - immunology; Peptides - metabolism; Physiological aspects; Proteasome Endopeptidase Complex; Protein Biosynthesis; Protein Structure, Tertiary; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Repetitive Sequences, Amino Acid; rev genes; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Transcription, Genetic; Transcripts (Written Records); Transfection; Translation; Tumor Cells, Cultured; Virology; Virus Latency; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1088902

The glycine-alanine repeat domain (GAr) of Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1) prevents major histocompatibility complex (MHC) class I-restricted presentation of EBNA1 epitopes to cytotoxic T cells. This effect has previously been attributed to the ability of GAr to inhibit its own proteasomal degradation. Here we show, both in vitro and in vivo, that GAr also inhibits messenger RNA translation of EBNA1 in cis and that this effect can be distinguished from its effect on proteasomal degradation. Hence, inhibition of messenger RNA translation, but not protein degradation, is essential to prevent antigen presentation on MHC class I molecules. Thus, by minimizing translation of the EBNA1 transcript, cells expressing EBNA1 avoid cytotoxic T cell recognition. At the same time, blocking degradation maintains the EBNA1 expression level.