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Windheim, M.* ; Southcombe, J.H.* ; Kremmer, E. ; Chaplin, L.* ; Urlaub, D.* ; Falk, C.S.* ; Claus, M.* ; Mihm, J.* ; Braithwaite, M.* ; Dennehy, K.* ; Renz, H.* ; Sester, M.* ; Watzl, C.* ; Burgert, H.G.*

A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions.

Proc. Natl. Acad. Sci. U.S.A. 110, E4884-E4893 (2013)
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The E3 transcription unit of human adenoviruses (Ads) encodes immunomodulatory proteins. Interestingly, the size and composition of the E3 region differs considerably among Ad species, suggesting that distinct sets of immunomodulatory E3 proteins may influence their interaction with the human host and the disease pattern. However, to date, only common immune evasion functions of species C E3 proteins have been described. Here we report on the immunomodulatory activity of a species D-specific E3 protein, E3/49K. Unlike all other E3 proteins that act on infected cells, E3/49K seems to target uninfected cells. Initially synthesized as an 80- to 100-kDa type I transmembrane protein, E3/49K is subsequently cleaved, with the large ectodomain (sec49K) secreted. We found that purified sec49K exhibits specific binding to lymphoid cell lines and all primary leukocytes, but not to fibroblasts or epithelial cells. Consistent with this binding profile and the molecular mass, the sec49K receptor was identified as the cell surface protein tyrosine phosphatase CD45. Antibody-blocking studies suggested that sec49K binds to the membrane proximal domains present in all CD45 isoforms. Functional studies showed that sec49K can suppress the activation and cytotoxicity of natural killer cells as well as the activation, signaling, and cytokine production of T cells. Thus, we have discovered an adenovirus protein that is actively secreted and describe immunomodulatory activities of an E3 protein uniquely expressed by a single Ad species.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Ad19a/Ad64; E3 protein shedding; epidemic keratoconjunctivitis; subversion of leukocytes; Epidemic Keratoconjunctivitis ; E3/19k Protein ; Intracellular Sequestration ; Monoclonal-antibodies ; Molecular Evolution ; Down-modulate ; Immune Cells ; Species-d ; T-cells ; Receptor
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 110, Issue: 50, Pages: E4884-E4893 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501793-001
PubMed ID 24218549
DOI 10.1073/pnas.1312420110
WOS ID WOS:000328061700011
Scopus ID 84890282771
Erfassungsdatum 2013-12-31
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