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Article

Fluorescent TAP as a Platform for Virus-Induced Degradation of the Antigenic Peptide Transporter

1
Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk, Abrahama 58, 80–307 Gdańsk, Poland
2
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1590; https://doi.org/10.3390/cells8121590
Received: 20 November 2019 / Revised: 3 December 2019 / Accepted: 5 December 2019 / Published: 7 December 2019
(This article belongs to the Special Issue Cell Biology of Viral Infections)
Transporter associated with antigen processing (TAP), a key player in the major histocompatibility complex class I-restricted antigen presentation, makes an attractive target for viruses that aim to escape the immune system. Mechanisms of TAP inhibition vary among virus species. Bovine herpesvirus 1 (BoHV-1) is unique in its ability to target TAP for proteasomal degradation following conformational arrest by the UL49.5 gene product. The exact mechanism of TAP removal still requires elucidation. For this purpose, a TAP-GFP (green fluorescent protein) fusion protein is instrumental, yet GFP-tagging may affect UL49.5-induced degradation. Therefore, we constructed a series of TAP-GFP variants using various linkers to obtain an optimal cellular fluorescent TAP platform. Mel JuSo (MJS) cells with CRISPR/Cas9 TAP1 or TAP2 knockouts were reconstituted with TAP-GFP constructs. Our results point towards a critical role of GFP localization on fluorescent properties of the fusion proteins and, in concert with the type of a linker, on the susceptibility to virally-induced inhibition and degradation. The fluorescent TAP platform was also used to re-evaluate TAP stability in the presence of other known viral TAP inhibitors, among which only UL49.5 was able to reduce TAP levels. Finally, we provide evidence that BoHV-1 UL49.5-induced TAP removal is p97-dependent, which indicates its degradation via endoplasmic reticulum-associated degradation (ERAD). View Full-Text
Keywords: TAP-GFP; fluorescent TAP platform; antigen presentation; MHC I; immune evasion; BoHV-1 UL49.5 TAP-GFP; fluorescent TAP platform; antigen presentation; MHC I; immune evasion; BoHV-1 UL49.5
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MDPI and ACS Style

Wąchalska, M.; Graul, M.; Praest, P.; Luteijn, R.D.; Babnis, A.W.; Wiertz, E.J.H.J.; Bieńkowska-Szewczyk, K.; Lipińska, A.D. Fluorescent TAP as a Platform for Virus-Induced Degradation of the Antigenic Peptide Transporter. Cells 2019, 8, 1590. https://doi.org/10.3390/cells8121590

AMA Style

Wąchalska M, Graul M, Praest P, Luteijn RD, Babnis AW, Wiertz EJHJ, Bieńkowska-Szewczyk K, Lipińska AD. Fluorescent TAP as a Platform for Virus-Induced Degradation of the Antigenic Peptide Transporter. Cells. 2019; 8(12):1590. https://doi.org/10.3390/cells8121590

Chicago/Turabian Style

Wąchalska, Magda, Małgorzata Graul, Patrique Praest, Rutger D. Luteijn, Aleksandra W. Babnis, Emmanuel J.H.J. Wiertz, Krystyna Bieńkowska-Szewczyk, and Andrea D. Lipińska 2019. "Fluorescent TAP as a Platform for Virus-Induced Degradation of the Antigenic Peptide Transporter" Cells 8, no. 12: 1590. https://doi.org/10.3390/cells8121590

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