Molecular Properties and Therapeutic Targeting of the EBV-Encoded Receptor BILF1

SIMPLE SUMMARY: The Epstein–Barr virus (EBV) is a γ-herpesvirus residing in over 90% of adults worldwide. Besides causing a benign glandular fever (infectious mononucleosis), EBV is also associated with a wide range of different types of cancers. This review will present these malignancies, current therapies, and summarize the present knowledge on an EBV-encoded oncogenic protein called BILF1. As a member of class A G protein–coupled receptors that are intrinsically successful drug targets, BILF1 will be discussed for its potential as future target in EBV-associated diseases. Finally, ongoing development of novel EBV-specific therapeutics is briefly outlined. ABSTRACT: The γ-herpesvirus Epstein–Barr Virus (EBV) establishes lifelong infections in approximately 90% of adults worldwide. Up to 1,000,000 people yearly are estimated to suffer from health conditions attributed to the infection with this virus, such as nasopharyngeal and gastric carcinomas as well as several forms of B, T and NK cell lymphoma. To date, no EBV-specific therapeutic option has reached the market, greatly reducing the survival prognoses of affected patients. Similar to other herpesviruses, EBV encodes for a G protein–coupled receptor (GPCR), BILF1, affecting a multitude of cellular signaling pathways. BILF1 has been identified to promote immune evasion and tumorigenesis, effectively ensuring a life-long persistence of EBV in, and driving detrimental health conditions to its host. This review summarizes the epidemiology of EBV-associated malignancies, their current standard-of-care, EBV-specific therapeutics in development, GPCRs and their druggability, and most importantly consolidates the findings of over 15 years of research on BILF1 in the context of EBV-specific drug development. Taken together, BILF1 constitutes a promising target for the development of novel EBV-specific therapeutics.