Epstein-Barr virus-encoded BILF1 orthologues from porcine lymphotropic herpesviruses display common molecular functionality

Mavri, Maša (avtor), Kubale, Valentina (avtor), Depledge, Daniel P. (avtor), Zuo, Jianmin (avtor), Huang, Christene A. (avtor), Breuer, Judith (avtor), Vrecl, Milka (avtor), Jarvis, Michael A. (avtor), Jarc Jovičić, Eva (avtor), Petan, Toni (avtor), Ehlers, Bernhard (avtor), Rosenkilde, Mette Marie (avtor), Spiess, Katja (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: Epstein-Barr virus, porcine lymphotropic herpesviruses (PLHV), BILF1, G protein signaling, MHC class I, drug target, post-transplant lymphoproliferative disease, in-vivo model
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: VF - Veterinarska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 16 str.
• Številčenje: Vol. 13, May, art. 862940
• PID: 20.500.12556/RUL-137258
• UDK: 636.09:616.9:578
• ISSN pri članku: 1664-2392
• DOI: 10.3389/fendo.2022.862940
• COBISS.SI-ID: 110428931
• Datum objave v RUL: 08.06.2022

Gradivo je del revije

• Naslov: Frontiers in endocrinology
• Založnik: Frontiers Media
• ISSN: 1664-2392
• COBISS.SI-ID: 3340154

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 26.05.2022