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Adenovirus E3/19K promotes evasion of NK cell recognition by intracellular sequestration of the NKG2D ligands, major histocompatibility complex class I chain-related proteins A and B
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McSharry, Brian P., Burgert, Hans-Gerhard , Owen, Douglas P., Stanton, Richard J., Prod'homme, Virginie, Sester, Martina, Koebernick, Katja, Groh, Veronika, Spies, Thomas, Cox, S. (Steven), Little, Ann-Margaret, Wang, Eddie C. Y., Tomasec, Peter and Wilkinson, Gavin W. G. (2008) Adenovirus E3/19K promotes evasion of NK cell recognition by intracellular sequestration of the NKG2D ligands, major histocompatibility complex class I chain-related proteins A and B. Journal of Virology, Vol.82 (No.9). pp. 4585-4594. doi:10.1128/JVI.02251-07
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Official URL: http://dx.doi.org/10.1128/JVI.02251-07
Abstract
The adenovirus (Ad) early transcription unit 3 (E3) encodes multiple immunosubversive functions that are presumed to facilitate the establishment and persistence of infection. Indeed, the capacity of E3/19K to inhibit transport of HLA class I (HIA-I) to the cell surface, thereby preventing peptide presentation to CD8(+) T cells, has long been recognized as a paradigm for viral immune evasion. However, HLA-I downregulation has the potential to render Ad-infected cells vulnerable to natural killer (NK) cell recognition. Furthermore, expression of the immediate-early Ad gene E1A is associated with efficient induction of ligands for the key NK cell-activating receptor NKG2D. Here we show that while infection with wild-type Ad enhances synthesis of the NKG2D ligands, major histocompatibility complex class I chain-related proteins A and B (MICA and MICB), their expression on the cell surface is actively suppressed. Both MICA and MICB are retained within the endoplasmic reticulum as immature endoglycosidase H-sensitive forms. By analyzing a range of cell lines and viruses carrying mutated versions of the E3 gene region, E3/19K was identified as the gene responsible for this activity. The structural requirements within E3/19K necessary to sequester MICA/B and HLA-I are similar. In functional assays, deletion of E3/19K rendered Ad-infected cells more sensitive to NK cell recognition. We report the first NK evasion function in the Adenoviridae and describe a novel function for E3/19K. Thus, E3/19K has a dual function: inhibition of T-cell recognition and NK cell activation.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR355 Virology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
| Library of Congress Subject Headings (LCSH): | Adenoviruses, Killer cells, Cellular recognition, Sequestration (Chemistry), Major histocompatibility complex | ||||
| Journal or Publication Title: | Journal of Virology | ||||
| Publisher: | American Society for Microbiology | ||||
| ISSN: | 0022-538X | ||||
| Official Date: | May 2008 | ||||
| Dates: |
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| Volume: | Vol.82 | ||||
| Number: | No.9 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 4585-4594 | ||||
| DOI: | 10.1128/JVI.02251-07 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Wellcome Trust (London, England), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Medical Research Council (Great Britain) (MRC) |
Data sourced from Thomson Reuters' Web of Knowledge
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