EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers
The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential fo...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-04-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/10/4/109 |
| _version_ | 1797762605176061952 |
|---|---|
| author | Joanna B. Wilson Evelyne Manet Henri Gruffat Pierre Busson Marc Blondel Robin Fahraeus |
| author_facet | Joanna B. Wilson Evelyne Manet Henri Gruffat Pierre Busson Marc Blondel Robin Fahraeus |
| author_sort | Joanna B. Wilson |
| collection | DOAJ |
| description | The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC) class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another means to cripple the virus. |
| first_indexed | 2024-03-12T19:29:48Z |
| format | Article |
| id | doaj.art-9c91a5ced6994e13b79f9a92a0056a8d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:29:48Z |
| publishDate | 2018-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9c91a5ced6994e13b79f9a92a0056a8d2023-08-02T04:37:34ZengMDPI AGCancers2072-66942018-04-0110410910.3390/cancers10040109cancers10040109EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated CancersJoanna B. Wilson0Evelyne Manet1Henri Gruffat2Pierre Busson3Marc Blondel4Robin Fahraeus5School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UKCIRI, Centre International de Recherche en Infectiologie, Team Oncogenic Herpesviruses, Inserm, Université Claude Bernard Lyon 1, CNRS, ENS-Lyon, Université de Lyon, F-69007 Lyon, FranceCIRI, Centre International de Recherche en Infectiologie, Team Oncogenic Herpesviruses, Inserm, Université Claude Bernard Lyon 1, CNRS, ENS-Lyon, Université de Lyon, F-69007 Lyon, FranceCNRS, UMR 8126, Gustave Roussy, Université Paris Sud, Université Paris-Saclay, F-94805 Villejuif, FranceUMR1078 “Génétique, Génomique Fonctionnelle et Biotechnologies”, Inserm, Université de Brest, EFS, IBSAM, CHU, F-29200 Brest, FranceInserm UMR1162, Université Paris 7, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, F-75010 Paris, FranceThe presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC) class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another means to cripple the virus.http://www.mdpi.com/2072-6694/10/4/109EBVEBNA1cancerdrug development |
| spellingShingle | Joanna B. Wilson Evelyne Manet Henri Gruffat Pierre Busson Marc Blondel Robin Fahraeus EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers Cancers EBV EBNA1 cancer drug development |
| title | EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers |
| title_full | EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers |
| title_fullStr | EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers |
| title_full_unstemmed | EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers |
| title_short | EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers |
| title_sort | ebna1 oncogenic activity immune evasion and biochemical functions provide targets for novel therapeutic strategies against epstein barr virus associated cancers |
| topic | EBV EBNA1 cancer drug development |
| url | http://www.mdpi.com/2072-6694/10/4/109 |
| work_keys_str_mv | AT joannabwilson ebna1oncogenicactivityimmuneevasionandbiochemicalfunctionsprovidetargetsfornoveltherapeuticstrategiesagainstepsteinbarrvirusassociatedcancers AT evelynemanet ebna1oncogenicactivityimmuneevasionandbiochemicalfunctionsprovidetargetsfornoveltherapeuticstrategiesagainstepsteinbarrvirusassociatedcancers AT henrigruffat ebna1oncogenicactivityimmuneevasionandbiochemicalfunctionsprovidetargetsfornoveltherapeuticstrategiesagainstepsteinbarrvirusassociatedcancers AT pierrebusson ebna1oncogenicactivityimmuneevasionandbiochemicalfunctionsprovidetargetsfornoveltherapeuticstrategiesagainstepsteinbarrvirusassociatedcancers AT marcblondel ebna1oncogenicactivityimmuneevasionandbiochemicalfunctionsprovidetargetsfornoveltherapeuticstrategiesagainstepsteinbarrvirusassociatedcancers AT robinfahraeus ebna1oncogenicactivityimmuneevasionandbiochemicalfunctionsprovidetargetsfornoveltherapeuticstrategiesagainstepsteinbarrvirusassociatedcancers |