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Epstein-Barr virus-encoded BILF1 orthologues from porcine lymphotropic herpesviruses display common molecular functionality
ID Mavri, Maša (Author), ID Kubale, Valentina (Author), ID Depledge, Daniel P. (Author), ID Zuo, Jianmin (Author), ID Huang, Christene A. (Author), ID Breuer, Judith (Author), ID Vrecl, Milka (Author), ID Jarvis, Michael A. (Author), ID Jarc Jovičić, Eva (Author), ID Petan, Toni (Author), ID Ehlers, Bernhard (Author), ID Rosenkilde, Mette Marie (Author), ID Spiess, Katja (Author)

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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 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.

Language:English
Keywords:Epstein-Barr virus, porcine lymphotropic herpesviruses (PLHV), BILF1, G protein signaling, MHC class I, drug target, post-transplant lymphoproliferative disease, in-vivo model
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:VF - Veterinary Faculty
Publication status:Published
Publication version:Version of Record
Year:2022
Number of pages:16 str.
Numbering:Vol. 13, May, art. 862940
PID:20.500.12556/RUL-137258 This link opens in a new window
UDC:636.09:616.9:578
ISSN on article:1664-2392
DOI:10.3389/fendo.2022.862940 This link opens in a new window
COBISS.SI-ID:110428931 This link opens in a new window
Publication date in RUL:08.06.2022
Views:681
Downloads:89
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Record is a part of a journal

Title:Frontiers in endocrinology
Publisher:Frontiers Media
ISSN:1664-2392
COBISS.SI-ID:3340154 This link opens in a new window

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:26.05.2022

Projects

Funder:ARRS - Slovenian Research Agency
Project number:P4-0053
Name:Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih

Funder:ARRS - Slovenian Research Agency
Funding programme:Young researchers

Funder:Other - Other funder or multiple funders
Funding programme:COST
Project number:CA 18133
Acronym:ERNEST

Funder:Other - Other funder or multiple funders
Funding programme:Danish Council for Independent Research, Postdoc grant

Funder:ARRS - Slovenian Research Agency
Project number:P1-0207
Name:Toksini in biomembrane

Funder:ARRS - Slovenian Research Agency
Project number:J7-1818
Name:Tarčno ciljanje metabolizma lipidnih kapljic za učinkovito zmanjševanje odpornosti rakavih celic na stres

Funder:ARRS - Slovenian Research Agency
Project number:Z3-2650
Name:Lipidne kapljice kot viri vnetnih lipidnih mediatorjev pri raku

Funder:EC - European Commission
Funding programme:H2020
Project number:682549
Name:Mumps VIRus EXploitation of the human adhesion receptor GPR125
Acronym:VIREX

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