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

Autor: Mavri M; Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia.; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Kubale V; Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia., Depledge DP; Department of Medicine, New York University School of Medicine, New York, NY, United States., Zuo J; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom., Huang CA; Department of Surgery, Division of Plastic & Reconstructive Surgery, Division of Transplant Surgery, Anschutz Medical Campus, University of Colorado, Denver, CO, United States., Breuer J; Division of Infection and Immunity, University College London, London, United Kingdom., Vrecl M; Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia., Jarvis MA; The Vaccine Group Ltd, Plymouth; and the University of Plymouth, Plymouth, United Kingdom., Jovičić EJ; Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia., Petan T; Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia., Ehlers B; Division 12, Measles, Mumps, Rubella, and Viruses Affecting Immunocompromised Patients, Robert Koch Institute, Berlin, Germany., Rosenkilde MM; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Spiess K; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 May 26; Vol. 13, pp. 862940. Date of Electronic Publication: 2022 May 26 (Print Publication: 2022).
DOI: 10.3389/fendo.2022.862940
Abstrakt: 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.
Competing Interests: Author MJ was employed, in part, by the company the Vaccine Group, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Mavri, Kubale, Depledge, Zuo, Huang, Breuer, Vrecl, Jarvis, Jovičić, Petan, Ehlers, Rosenkilde and Spiess.)
Databáze: MEDLINE
Externí odkaz: