Epstein-Barr Virus-Encoded BILF1 Orthologues From Porcine Lymphotropic Herpesviruses Display Common Molecular Functionality

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

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 Gαi 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.

Original languageEnglish
Article number862940
JournalFrontiers in Endocrinology
Number of pages16
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Mavri, Kubale, Depledge, Zuo, Huang, Breuer, Vrecl, Jarvis, Jovičić, Petan, Ehlers, Rosenkilde and Spiess.

    Research areas

  • BILF1, drug target, Epstein-Barr virus, G protein signaling, in-vivo model, MHC class I, porcine lymphotropic herpesviruses (PLHV), post-transplant lymphoproliferative disease

ID: 314075033