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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Renz, Harald Braithwaite, Myles Watzl, Carsten Falk, Christine S. Sester, Martina Burgert, Hans-gerhard Claus, Maren Chaplin, Lucy Windheim, Mark Urlaub, Doris Southcombe, Jennifer H. Kremmer, Elisabeth Mihm, Janine Dennehy, Kevin |
| Description | Author Affiliation: Windheim M ( School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adenovirus E3 Proteins Metabolism Adenoviruses, Human Antigens, CD45 Immunomodulation Immunology Leukocytes Genetics Blotting, Western Cell Line, Tumor Cloning, Molecular Electrophoresis, Polyacrylamide Gel HEK293 Cells Immunoprecipitation Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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