title: EBV, the human host, and the 7TM receptors: defense or offense?
abstract: Being present in around 90% of the worldwide population, Epstein-Barr virus (EBV) is an exceptionally prevalent virus. This highly successful virus establishes a latent infection in resting memory B cells and is maintained in a balance between viral homeostasis on one side and antiviral defense of the immune system on the other side. The life cycle of EBV is dependent on many viral proteins, but EBV also regulates a number of endogenous proteins. 7TM receptors and ligands of viral and host origin are examples of such proteins. 7TM receptors are highly druggable and they are among the most popular class of investigational drug targets. The 7TM receptor encoded by EBV-BILF1, is known to downregulate cell surface MHC class I expression as part of the immune evasion strategy of EBV. However, the functional impact of the relationship between EBV and the regulated endogenous 7TM receptors and ligands is still unclear. This is for instance the case for the most upregulated 7TM receptor EBI2 (EBV-induced gene 2 or GPR183). Whereas some regulated genes have been suggested to be involved in the EBV life cycle, others could also be important for the antiviral immune defense. As many of these 7TM receptors and ligands have been shown to be modulated in EBV-associated diseases, targeting these could provide an efficient and specific way to inhibit EBV-associated disease progression. Here, we will review current knowledge on EBV infection, the immune defense against EBV and 7TM receptors and ligands being either encoded or manipulated by EBV.
authors.affiliation: Faculty of Health and Medical Sciences, Department of Neuroscience and Pharmacology, Laboratory for Molecular Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristine Niss
authors.initials: KN
authors.lastname: Arfelt
authors.affiliation: Faculty of Health and Medical Sciences, Department of Neuroscience and Pharmacology, Laboratory for Molecular Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Suzan
authors.initials: S
authors.lastname: Fares
authors.affiliation: Faculty of Health and Medical Sciences, Department of Neuroscience and Pharmacology, Laboratory for Molecular Pharmacology, University of Copenhagen, Copenhagen, Denmark. Electronic address: rosenkilde@sund.ku.dk.
authors.forename: Mette M
authors.initials: MM
authors.lastname: Rosenkilde
mesh_terms: D020031:Epstein-Barr Virus Infections / Q000821:virology; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled; D014764:Viral Proteins
keywords: 7TM; BILF1; EBI2; EBV; GPCR; GPR183; chemokine; oxysterol; virus-encoded receptors; virus-induced receptors