Epstein-Barr Virus-Encoded BILF1 Orthologues From Porcine Lymphotropic Herpesviruses Display Common Molecular Functionality
Year: 2022
Type: article
Abstract: 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.
Source: Frontiers in Endocrinology
Institutions: University of Copenhagen, University of Ljubljana, New York University, University of Birmingham, University of Colorado Anschutz, University of Colorado Denver, University College London, University of Plymouth, Jožef Stefan Institute, Jožef Stefan International Postgraduate School, Robert Koch Institute
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: Toxins and Biomembranes, Mumps VIRus EXploitation of the human adhesion receptor GPR125, Targeting lipid droplets to reduce cancer cell resistance to stress, Lipid droplets as sources of inflammatory lipid mediators in cancer, G5740621926, Endocrine, immune and enzyme responses in healthy and sick animals
OpenAlex ID: W4282053035