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- Title
Inhibition of B cell receptor signaling induced by the human adenovirus species D E3/49K protein.
- Authors
Hildenbrand, Andreas; Cramer, Precious; Bertolotti, Milena; Kaiser, Nathalie Sophia; Kläsener, Kathrin; Nickel, Clara Muriel; Reth, Michael; Heim, Albert; Hengel, Hartmut; Burgert, Hans-Gerhard; Ruzsics, Zsolt
- 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. 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.
- Subjects
B cell receptors; MEMBRANE proteins; VIRAL proteins; PROTEIN-tyrosine phosphatase; KILLER cells; T cell receptors
- Publication
Frontiers in Immunology, 2024, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2024.1432226