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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1432226

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

Provisionally accepted
Andreas Hildenbrand Andreas Hildenbrand 1,2Precious Cramer Precious Cramer 3Milena Bertolotti Milena Bertolotti 4,5Nathalie S. Kaiser Nathalie S. Kaiser 1,2Kathrin Kläsener Kathrin Kläsener 2,6Clara M. Nickel Clara M. Nickel 1,2Michael Reth Michael Reth 2,6Albert Heim Albert Heim 7Hartmut Hengel Hartmut Hengel 1,2Hans-Gerhard Burgert Hans-Gerhard Burgert 1,2Zsolt Ruzsics Zsolt Ruzsics 1,2*
  • 1 Institute of Virology, Freiburg University Medical Center, Freiburg, Germany
  • 2 Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • 3 Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany
  • 4 Signaling Research Centers CIBSS and BIOSS, University of Freiburg, Freiburg, Germany
  • 5 Navita S.r.l., University of Eastern Piedmont A. Avogadro, Novara, Italy
  • 6 Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, Germany
  • 7 Institute of Virology, Hannover Medical School, Hannover, Lower Saxony, Germany

The final, formatted version of the article will be published soon.

    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. 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. However, 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. In conclusion, we identified B cells as new direct target of E3/49K-mediated immune modulation, representing a novel viral immunosubversive mechanism.

    Keywords: adenovirus 1, E3/49K 2, immunoevasion 3, BCR signaling 4, CD45 5

    Received: 13 May 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Hildenbrand, Cramer, Bertolotti, Kaiser, Kläsener, Nickel, Reth, Heim, Hengel, Burgert and Ruzsics. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zsolt Ruzsics, Institute of Virology, Freiburg University Medical Center, Freiburg, 79104, Germany

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