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Inhibition of B cell receptor signaling induced by the human adenovirus species D E3/49K protein.
- Source :
-
Frontiers in immunology [Front Immunol] 2024 Jul 30; Vol. 15, pp. 1432226. Date of Electronic Publication: 2024 Jul 30 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: We identified B cells as new direct target of E3/49K-mediated immune modulation, representing a novel viral immunosubversive mechanism.<br />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.<br /> (Copyright © 2024 Hildenbrand, Cramer, Bertolotti, Kaiser, Kläsener, Nickel, Reth, Heim, Hengel, Burgert and Ruzsics.)
- Subjects :
- Humans
Adenovirus Infections, Human immunology
Adenovirus Infections, Human virology
Adenovirus Infections, Human metabolism
HEK293 Cells
Receptors, Antigen, B-Cell metabolism
Receptors, Antigen, B-Cell immunology
Signal Transduction immunology
Leukocyte Common Antigens metabolism
Leukocyte Common Antigens immunology
Adenoviruses, Human immunology
Adenovirus E3 Proteins immunology
Adenovirus E3 Proteins metabolism
Adenovirus E3 Proteins genetics
B-Lymphocytes immunology
B-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 39139562
- Full Text :
- https://doi.org/10.3389/fimmu.2024.1432226