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

Frontiers in Endocrinology

Judith Breuer¹  Toni Petan²  Maša Mavri³  Daniel P. Depledge⁴  Bernhard Ehlers⁵  Mette M. Rosenkilde⁵  Christene A. Huang⁶  Katja Spiess⁷  Milka Vrecl⁸  Jianmin Zuo⁹  Michael A. Jarvis^1,10  Valentina Kubale^1,10  Eva Jarc Jovičić^1,11 

[1] Reconstructive Surgery, Division of Transplant Surgery, Anschutz Medical Campus, University of Colorado, Denver, CO, United States;and the University of Plymouth, Plymouth, United Kingdom;Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Medicine, New York University School of Medicine, New York, NY, United States;Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia;;Department of Surgery, Division of Plastic &Division 12, Measles, Mumps, Rubella, and Viruses Affecting Immunocompromised Patients, Robert Koch Institute, Berlin, Germany;Division of Infection and Immunity, University College London, London, United Kingdom;Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia;The Vaccine Group Ltd, Plymouth;

关键词: Epstein-Barr virus;    porcine lymphotropic herpesviruses (PLHV);    BILF1;    G protein signaling;    MHC class I;    drug target;   

DOI  :  10.3389/fendo.2022.862940

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown