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

Abstract

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.