Patterns of human and porcine gammaherpesvirus-encoded BILF1 receptor endocytosis

Mavri, Maša (avtor), Glisic, Sanja (avtor), Sencanski, Milan (avtor), Vrecl, Milka (avtor), Rosenkilde, Mette Marie (avtor), Spiess, Katja (avtor), Kubale, Valentina (avtor)

Background: The viral G protein-coupled receptor (vGPCR) BILF1 encoded by the Epstein-Barr virus (EBV) is an oncogene and immunoevasin and can downregulate MHC-I molecules at the surface of infected cells. MHC-I downregulation, which presumably occurs through co-internalization with EBV-BILF1, is preserved among BILF1 receptors, including the three BILF1 orthologues encoded by porcine lymphotropic herpesviruses (PLHV BILFs). This study aimed to understand the detailed mechanisms of BILF1 receptor constitutive internalization, to explore the translational potential of PLHV BILFs compared to EBV-BILF1. Methods: A novel real-time fluorescence resonance energy transfer (FRET)-based internalization assay combined with dominant-negative variants of dynamin-1 (Dyn K44A) and the chemical clathrin inhibitor Pitstop2 in HEK-293A cells was used to study the effect of specific endocytic proteins on BILF1 internalization. Bioluminescence resonance energy transfer (BRET)-saturation analysis was used to study BILF1 receptor interaction with β-arrestin2 and Rab7. In addition, a bioinformatics approach Informational spectrum method (ISM) was used to investigate the interaction affinity of BILF1 receptors with β-arrestin2, AP-2 and caveolin-1. Results: We identified dynamin-dependent, clathrin-mediated constitutive endocytosis for all BILF1 receptors. The observed interaction affinity between BILF1 receptors and caveolin-1 and the decreased internalization in the presence of a dominant-negative variant of caveolin-1 (Cav S80E) indicated the involvement of caveolin-1 in BILF1 trafficking. Furthermore, after BILF1 internalization from the plasma membrane, both the recycling and degradation pathways are proposed for BILF1 receptors. Conclusions: The similarity in the internalization mechanisms observed for EBV-BILF1 and PLHV1-2 BILF1 provide a foundation for further studies exploring a possible translational potential for PLHVs, as proposed previously, and provides new information about receptor trafficking.

• Jezik: Angleški jezik
• Ključne besede: Herpesvirus 4, human, Dynamins, Caveolins, beta-Arrestins
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: VF - Veterinarska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Datum objave: 01.01.2023
• Leto izida: 2023
• Št. strani: Str. 1-19
• Številčenje: Vol. 28, [artlice no.] 14
• PID: 20.500.12556/RUL-144509
• UDK: 577
• ISSN pri članku: 1689-1392
• DOI: 10.1186/s11658-023-00427-y
• COBISS.SI-ID: 141009411
• Datum objave v RUL: 27.02.2023

Gradivo je del revije

• Naslov: Cellular and molecular biology letters. international scientific journal
• Skrajšan naslov: Cell. Mol. Biol. Lett.
• Založnik: University of Wrocław
• ISSN: 1689-1392
• COBISS.SI-ID: 3249585

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Projekti

• Financer: MESTD - Ministry of Education, Science and Technological Development of Republic of Serbia
• Številka projekta: 451-03-47/2023-01/200017

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Slovenian-Serbian bilateral project
• Številka projekta: BI-RS/20-21-045