Inhibition of B cell receptor signaling induced by the human adenovirus species D E3/49K protein.

Autor:	Hildenbrand A; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany., Cramer P; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany., Bertolotti M; Signaling Research Centers CIBSS and BIOSS, University of Freiburg, Freiburg, Germany.; Navita S.r.l., University of Eastern Piedmont A. Avogadro, Novara, Italy., Kaiser NS; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kläsener K; Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Nickel CM; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany., Reth M; Signaling Research Centers CIBSS and BIOSS, University of Freiburg, Freiburg, Germany.; Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Heim A; Institute of Virology, Hannover Medical School, Hannover, Germany., Hengel H; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany., Burgert HG; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ruzsics Z; Institute of Virology, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jul 30; Vol. 15, pp. 1432226. Date of Electronic Publication: 2024 Jul 30 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1432226
Abstrakt:	Introduction: The early transcription unit 3 (E3) of human adenoviruses (HAdVs) encodes several immunoevasins, including the E3/49K protein, which is unique for species D of HAdVs. It is expressed as surface transmembrane protein and shed. E3/49K of HAdV-D64 binds to the protein tyrosine phosphatase surface receptor CD45, thereby modulating activation of T and NK cells. Methods: Considering that E3/49K represents the most polymorphic viral protein among species D HAdVs, we demonstrate here that all tested E3/49K orthologs bind to the immunologically important regulator CD45. Thus, this feature is conserved regardless of the pathological associations of the respective HAdV types. Results: It appeared that modulation of CD45 is a unique property restricted to HAdVs of species D. Moreover, E3/49K treatment inhibited B cell receptor (BCR) signaling and impaired BCR signal phenotypes. The latter were highly comparable to B cells having defects in the expression of CD45, suggesting E3/49K as a potential tool to investigate CD45 specific functions. Conclusion: We identified B cells as new direct target of E3/49K-mediated immune modulation, representing a novel viral immunosubversive mechanism. Competing Interests: Author MB was employed by Navita S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Hildenbrand, Cramer, Bertolotti, Kaiser, Kläsener, Nickel, Reth, Heim, Hengel, Burgert and Ruzsics.)
Databáze:	MEDLINE
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