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. ISSN 0022-538X

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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
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR355 Virology
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
Date:	May 2008
Volume:	Vol.82
Number:	No.9
Number of Pages:	10
Page Range:	pp. 4585-4594
Identification Number:	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)
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URI:	http://wrap.warwick.ac.uk/id/eprint/30203

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