@article{179221,
  keywords = {Animals, Base Sequence, Humans, Molecular Sequence Data, RNA, Messenger, Cell Line, Recombinant Fusion Proteins, Amino Acid Sequence, beta-Galactosidase, Mice, Open Reading Frames, Peptides, Viral Proteins, T-Lymphocytes, Cytotoxic, Antigen Presentation, Epstein-Barr Virus Nuclear Antigens},
  author = {Martine Ossevoort and Arnaud Zaldumbide and Aartjan Te Velthuis and Mark Melchers and Maaike Ressing and Emmanuel Wiertz and Rob Hoeben},
  title = {The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis},
  abstract = { Herpesviruses employ many mechanisms to evade the immune response, allowing them to persist life-long in their hosts. The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) and, more recently, the latency-associated nuclear antigen 1 (LANA-1) of the Kaposi Sarcoma Herpesvirus have been shown to function as in cis-acting inhibitors of antigen presentation. In both proteins, long simple repeat elements are responsible for the inhibition, but the sequences of these repeats are strongly dissimilar. Intriguingly, EBNA-1 mRNA contains a large nested open reading frame that codes for a 40.7kDa strongly acidic protein, in addition to the full-length EBNA-1. This protein, here called pGZr, has a 230 amino-acids long glycine, glutamine, and glutamic acid-rich repeat ({\textquoteright}GZ{\textquoteright} repeat), highly similar (65\% amino-acid identity) to the acidic repeat of LANA-1. To evaluate if pGZr, like EBNA-1 and LANA-1, can inhibit antigen presentation in cis, we fused the nested ORF with the E. coli-derived LacZ gene encoding beta-galactosidase. Whereas cells producing the unmodified beta-galactosidase readily present the H-2L(d)-restricted CTL epitope TPHPARIGL, which resides in the C-terminal region of beta-galactosidase, cells producing the pGZr-beta-galactosidase fusion protein do not. Also shorter fragments of the repeat can inhibit peptide presentation. Even though the physiological function of pGZr remains to be elucidated, the GZ-repeat protein may be valuable as inhibitor of presentation of antigenic peptides derived from transgenes in gene therapy. },
  year = {2007},
  journal = {Mol Immunol},
  volume = {44},
  pages = {3588-96},
  month = {07/2007},
  issn = {0161-5890},
  doi = {10.1016/j.molimm.2007.03.005},
  language = {eng},
}