Maša Mavri (Avtor), Valentina Kubale (Avtor), Daniel P. Depledge (Avtor), Jianmin Zuo (Avtor), Christene A. Huang (Avtor), Judith Breuer (Avtor), Katja Spiess (Avtor), Milka Vrecl (Avtor), Michael A. Jarvis (Avtor), Eva Jarc (Avtor), Toni Petan (Avtor), Bernhard Ehlers (Avtor), Mette Marie Rosenklide (Avtor)

Povzetek

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.

Ključne besede

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

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: IJS - Institut Jožef Stefan
UDK: 636.09:616.9:578
COBISS: 110428931 Povezava se bo odprla v novem oknu
ISSN: 1664-2392
Št. ogledov: 110
Št. prenosov: 50
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarne ključne besede: Epstein-Barr Virus Infections;veterinary;Herpesviridae;GTP-Binding Proteins;Swine;
Vrsta dela (COBISS): Članek v reviji
Strani: art. 862940, str. 1-16
Zvezek: ǂVol. ǂ13
Čas izdaje: 2022
DOI: 10.3389/fendo.2022.862940
ID: 15574442