Adenovirus vector delivery stimulates natural killer cell recognition
Open accessAbstract
We report that delivery of first-generation replication-deficient adenovirus (RDAd) vectors into primary human fibroblasts is associated with the induction of natural killer (NK) cell-mediated cytolysis in vitro. RDAd vector delivery induced cytolysis by a range of NK cell populations including the NK cell clone NKL, primary polyclonal NK lines and a proportion of NK clones (36 %) in autologous HLA-matched assays. Adenovirus-induced cytolysis was inhibited by antibody blocking of the NK-activating receptor NKG2D, implicating this receptor in this function. NKG2D is ubiquitously expressed on NK cells and CD8+ T cells. Significantly, γ-irradiation of the vector eliminated the effect, suggesting that breakthrough expression from the vector induces at least some of the pro-inflammatory responses of unknown aetiology following the application of RDAd vectors during in vivo gene delivery.
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The candidate signature gene RAET1G is one of the few genes that could encode a ligand recognized by NKG2D proteins in response to stress and infections.
“Remarkably, the candidate signature gene RAET1G is one of the few genes that could encode a ligand recognized by NKG2D proteins in response to stress and infections (Eagle and Trowsdale, 2007; Tomasec et al., 2007; Lanier, 2015).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Tomasec et al., 2007
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BackgroundNKG2D Is Required for NK Cell Activation and Function in Response to E1-Deleted Adenovirus
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- Authors
- Tomasec, P., Wang, E. C. Y., Groh, V., Spies, T., McSharry, B. P., Aicheler, R. J., Stanton, R. J., & Wilkinson, G. W. G.
- Affiliations
- Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK
- Cardiff University (GB)
- Fred Hutch Cancer Center (US)
- ORCID
- Venue
- Journal of General Virology
- Publisher
- Microbiology Society
- Published
- 2007-04-01
- Volume
- 88
- Issue
- 4
- Pages
- 1103-1108
- ISSN
- 0022-1317 (ISSN-L)
- 1465-2099
- PMC
- PMC2841999
- OpenAlex
- W1964769874
- Cited by
- 18
- References
- 46
- Citations by year
- 2025: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 2 · 2014: 1 · 2012: 1
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Journal of General Virology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Charles Sturt University Research Output (CRO) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- natural killer cells, NK cell-mediated cytolysis, NKG2D, fibroblasts, gene therapy vectors, gamma irradiation, pro-inflammatory response, CD8+ T cells
- MeSH terms
- Adenoviridae, Cells, Cultured, Cytotoxicity, Immunologic, Fibroblasts, Genetic Vectors, Humans, Killer Cells, Natural, Receptors, Immunologic, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily K
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