Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1.
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.
Yin
Yili
Y
Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Manoury
Bénédicte
B
Fåhraeus
Robin
R
D020816:Amino Acid Motifs; D017951:Antigen Presentation; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D017735:Virus Latency; D019892:eIF-2 Kinase / Q000378:metabolism
D019309:Epstein-Barr Virus Nuclear Antigens; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D010455:Peptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019892:eIF-2 Kinase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C417029:EBV-encoded nuclear antigen 1