Viral hijacking of human receptors through heterodimerization.
Epstein-Barr virus (EBV) is a human herpesvirus that primarily infects B lymphocytes and is associated with tumor development. Like other herpesviruses, EBV has pirated and modified host genes encoding important regulatory cellular proteins to take over cellular control after infection. One of these genes (BILF1) encodes a G protein-coupled receptor (GPCR). It is currently accepted that GPCRs exist and function as dimers. B lymphocyte migration and functioning is regulated by chemokines acting on their cognate receptors. In this study, we show that BILF1 heterodimerizes with various chemokine receptors using BRET, trFRET and co-immunoprecipitation. Importantly, heterodimerization of BILF1 with chemokine receptors may alter the responsiveness of B lymphocytes to chemokines thereby altering homing and homeostasis of infected B lymphocytes and might be essential for EBV dissemination and/or involved in EBV-induced pathogenesis.
Vischer
Henry F
HF
Division of Medicinal Chemistry, Faculty of Sciences, Leiden/Amsterdam Center for Drug Research, VU University Amsterdam, Amsterdam, The Netherlands. vischer@few.vu.nl
Nijmeijer
Saskia
S
Smit
Martine J
MJ
Leurs
Rob
R
D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology; D002465:Cell Movement; D019281:Dimerization; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008163:Luminescent Measurements; D019707:Receptors, Chemokine / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
C495131:BILF1 protein, Epstein-Barr virus; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D014764:Viral Proteins