20.500.12556/RUL-137258 Epstein-Barr virus-encoded BILF1 orthologues from porcine lymphotropic herpesviruses display common molecular functionality Infection of immunosuppressed transplant patients with the human γ-herpesvirus Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD), an often fatal complication. Immunosuppressed miniature pigs infected with γ-herpesvirus porcine lymphotropic herpesvirus 1 (PLHV1) develop a similar disease, identifying pigs as a potential preclinical model for PTLD in humans. BILF1 is a G protein-coupled receptor (GPCR) encoded by EBV with constitutive activity linked to tumorigenesis and immunoevasive function downregulating MHC-I. In the present study, we compared BILF1-orthologues encoded by the three known PLHVs (PLHV1-3) with EBV-BILF1 to determine pharmacological suitability of BILF1 orthologues as model system to study EBV-BILF1 druggability. Cell surface localization, constitutive internalization, and MHC-I downregulation as well as membrane proximal constitutive Gα$_i$ signaling patterns were conserved across all BILFs. Only subtle differences between the individual BILFs were observed in downstream transcription factor activation. Using Illumina sequencing, PLHV1 was observed in lymphatic tissue from PTLD-diseased, but not non-diseased pigs. Importantly, these tissues showed enhanced expression of PLHV1-BILF1 supporting its involvement in PTLD infection. Epstein-Barr virus porcine lymphotropic herpesviruses (PLHV) BILF1 G protein signaling MHC class I drug target post-transplant lymphoproliferative disease in-vivo model true false true Angleški jezik Ni določen Članek v reviji 2022-06-08 12:54:11 2022-06-08 12:54:11 2022-09-15 04:14:51 0000-00-00 00:00:00 2022 0 0 16 str. May, art. 862940 Vol. 13 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 636.09:616.9:578 1664-2392 10.3389/fendo.2022.862940 110428931 Epstein-barr-Kubale.pdf Epstein-barr-Kubale.pdf 1 EACEA990D8747A699ABF89AEEAFF4E72 ed16cc4171975caedc9c11e5b9477c8f0a46e395ba1bfbf4663763f592f6cb19 fffba26f-e71d-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157155 https://www.frontiersin.org/articles/10.3389/fendo.2022.862940/full 0 2c49b886-e719-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157154 Veterinarska fakulteta 0 0 0