The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis.
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 fun...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1826257008428318720 |
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| author | Ossevoort, M Zaldumbide, A te Velthuis, A Melchers, M Ressing, M Wiertz, E Hoeben, R |
| author_facet | Ossevoort, M Zaldumbide, A te Velthuis, A Melchers, M Ressing, M Wiertz, E Hoeben, R |
| author_sort | Ossevoort, M |
| collection | OXFORD |
| description | 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 ('GZ' 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. |
| first_indexed | 2024-03-06T18:11:19Z |
| format | Journal article |
| id | oxford-uuid:031dfe65-da29-4b71-b2ad-fb0b2a78e666 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:11:19Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:031dfe65-da29-4b71-b2ad-fb0b2a78e6662022-03-26T08:44:16ZThe nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:031dfe65-da29-4b71-b2ad-fb0b2a78e666EnglishSymplectic Elements at Oxford2007Ossevoort, MZaldumbide, Ate Velthuis, AMelchers, MRessing, MWiertz, EHoeben, RHerpesviruses 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 ('GZ' 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. |
| spellingShingle | Ossevoort, M Zaldumbide, A te Velthuis, A Melchers, M Ressing, M Wiertz, E Hoeben, R The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis. |
| 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. |
| title_full | The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis. |
| title_fullStr | The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis. |
| title_full_unstemmed | The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis. |
| title_short | The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA encodes a protein capable of inhibiting antigen presentation in cis. |
| title_sort | nested open reading frame in the epstein barr virus nuclear antigen 1 mrna encodes a protein capable of inhibiting antigen presentation in cis |
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