VirGO · Studying a VIRal Gpcr in Oncogenesis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-09-14 → 2023-04-14
- EU contribution
- €196,591
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
VIRGO: Studying a VIRal Gpcr in Oncogenesis
The Epstein-Barr virus (EBV) is a herpesvirus which infects more than 90% of people worldwide. While in the majority of cases the virus induces an asymptomatic infection, in a small percentage of persons, the virus contributes to malignant transformation, causing at least nine types of cancer, including Burkitt lymphoma (BL), one of the most important EBV-associated paediatric tumours. Totally, EBV accounts for 200,000 new cancer cases and over 142,000 deaths worldwide every year. However, deaths from EBV-associated cancers have increased by 14.6% since 1990 and are predicted to increase further. Although EBV is a problem of worldwide importance, no vaccine or antiviral drug has yet been approved, in part due to the limited number of targetable virus proteins present in EBV-driven cancers. Recent scientific data suggest that the tumour cells of EBV-associated cancers such as BL express the EBV-encoded BILF1, a constitutively active G-protein coupled receptor (GPCR). GPCRs are currently the most effective class of pharmacological targets for the treatment of human conditions, and they are also becoming important anti-cancer targets. EBV-encoded BILF1 shows many similarities with other viral GPCRs and might be a realistic therapeutic target for EBV-associated malignancies. However, its function is largely unknown. This European Fellowship has allowed a young researcher of proven ability to investigate the role of BILF1 in lymphomagenesis in an internationally renowned laboratory. Specifically, the EU-funded VirGO project aimed to: (i) explore the role of BILF1 in EBV-negative germinal centre B-cell (GC-B) transformation, the progenitor of BL; (ii) identify how BILF1 contributes to the established phenotype of BL cells; (iii) and link these phenotypes to BL primary tumour pathological features and to patient response to therapy.
Data: CORDIS, © European Union
Project objective
The Epstein–Barr virus (EBV) is widespread in all human communities. While most people carry EBV as a life-long asymptomatic infection, in some people, EBV contributes to malignant transformation and is responsible for ~200,000 new cancer cases/year. Small molecule inhibitors targeting viral proteins could be an effective option to treat people with EBV-associated cancers. However, no such drugs exists which in part reflects the limited repertoire of targetable virus proteins present in EBV-driven cancers. Recently, the Experienced Researcher (ER) has shown that the tumour cells of EBV-associated cancers such as Burkitt lymphoma (BL), express the EBV-encoded BILF1, a constitutively active G-protein coupled receptor (GPCR). Furthermore, preliminary data by the ER indicate that BILF1 partially recapitulates the aberrant transcriptional programme of BL and is likely to do so through activation of oncogenic cell signalling pathways that include AKT-mTOR. These data suggest that BILF1 could be a realistic therapeutic target, raising the possibility of advancing the development of anti-viral drugs to treat EBV-related tumours; GPCRs are the most successful class of drug target for the treatment of human disorders and are emerging as anti-cancer targets. In this project the ER will harness new models of B cell lymphomagenesis available in the host laboratory to: 1) Explore the role of BILF1in the transformation of germinal centre B cells; the progenitors of BL; 2) Identify how BILF1 contributes to the established phenotype of BL cells; and 3) Link these phenotypes to pathological features of the primary tumour and to patient response to therapy. Thus, the Fellowship will significantly advance knowledge of the mechanisms of EBV-mediated oncogenesis, in turn paving the way for the development of new EBV-targeted small molecule drugs. The ER will emerge from this project with a new advanced skill-set and the capability to launch her own high level scientific research.
Original text from CORDIS.
Participants
- UNIVERSITY OF LIMERICK · LimerickCoordinatorIreland
Links
Data: CORDIS, © European Union