Epstein Barr Virus-Encoded EBNA1 Interference with MHC Class I Antigen Presentation Reveals a Close Correlation between mRNA Translation Initiation and Antigen Presentation

PLoS Pathogens

Sebastien Apcher¹  Robin Fåhraeus¹  Chrysoula Daskalogianni¹  Benedicte Manoury² 

[1] Cibles Thérapeutiques, INSERM U940, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, Paris, France;Institute Curie, Paris, France

关键词: Antigen presentation;    Messenger RNA;    Translation initiation;    Major histocompatibility complex;    Internal ribosome entry site;    Protein translation;    MHC class I genes;    Ova;   

DOI  :  10.1371/journal.ppat.1001151

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viruses are known to employ different strategies to manipulate the major histocompatibility (MHC) class I antigen presentation pathway to avoid recognition of the infected host cell by the immune system. However, viral control of antigen presentation via the processes that supply and select antigenic peptide precursors is yet relatively unknown. The Epstein-Barr virus (EBV)-encoded EBNA1 is expressed in all EBV-infected cells, but the immune system fails to detect and destroy EBV-carrying host cells. This immune evasion has been attributed to the capacity of a Gly-Ala repeat (GAr) within EBNA1 to inhibit MHC class I restricted antigen presentation. Here we demonstrate that suppression of mRNA translation initiation by the GAr in cis is sufficient and necessary to prevent presentation of antigenic peptides from mRNAs to which it is fused. Furthermore, we demonstrate a direct correlation between the rate of translation initiation and MHC class I antigen presentation from a certain mRNA. These results support the idea that mRNAs, and not the encoded full length proteins, are used for MHC class I restricted immune surveillance. This offers an additional view on the role of virus-mediated control of mRNA translation initiation and of the mechanisms that control MHC class I restricted antigen presentation in general.

【 授权许可】

CC BY