A detection system for viral dsDNA?

Stacey, K. J., Roberts, T. L., Idris, A., Dunn, A., Hume, D. A. and Ross, I. L. (2005). A detection system for viral dsDNA?. In: Tissue Antigens. Proceedings of: Genetics and The Immune Response'Abstracts of the 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop. 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop, Melbourne, Australia, (550-551). 29 November - 2 December 2005. doi:10.1111/j.1399-0039.2005.00523.x


Author Stacey, K. J.
Roberts, T. L.
Idris, A.
Dunn, A.
Hume, D. A.
Ross, I. L.
Title of paper A detection system for viral dsDNA?
Conference name 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop
Conference location Melbourne, Australia
Conference dates 29 November - 2 December 2005
Proceedings title Tissue Antigens. Proceedings of: Genetics and The Immune Response'Abstracts of the 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop   Check publisher's open access policy
Journal name Tissue Antigens   Check publisher's open access policy
Place of Publication Copenhagan, Denmark
Publisher John Wiley & Sons
Publication Year 2005
DOI 10.1111/j.1399-0039.2005.00523.x
ISSN 0001-2815
Volume 66
Issue 5
Start page 550
End page 551
Total pages 1
Language eng
Abstract/Summary The simplicity and diversity of viruses makes characteristic viral molecules difficult for the innate immune system to define. Activation by viral double stranded (ds) RNA has been known for many years, and this occurs through both the endosomal receptor TLR3 and cytoplasmic receptors. Recently other nucleic acids have emerged as important indicators of viral infection: CpG motif-containing DNA and viral single stranded (ss) RNAs are recognised in the endosomal compartment by TLR9 and TLR7 respectively. We propose a novel mechanism exists for recognition of viral dsDNA. Macrophages respond to transfected ds but not ssDNA with MHC I upregulation, secretion of IL-6 and TNF-a, and apoptotic death. In primary macrophages, death following electroporation is profound, and is dsDNA dependent. Cell death is independent of TLR9. The effect is sequence-independent, but dependent on the length of DNA, with maximal death seen above 1 kb. Activation of caspase 3 within 10 minutes after electroporation with dsDNA shows that there is a specific rapid response to transfected DNA. Relevance of this phenomenon to anti-viral defence is suggested by published work showing that retroviral superinfections resulting in accumulation of unintegrated cytoplasmic DNA cause apoptosis. Although DNA damage pathways could be involved in the response, we have found that p53, DNA-PK and ATM functions are not required for cell death. We are characterising sequence non-specific DNA binding proteins as potential receptors for foreign dsDNA. Apart from possible relevance to detection of pathogen DNA, elucidation of this pathway is relevant to TLR9-independent cellular activation in DNA vaccination and improving gene therapy.
Subjects 06 Biological Sciences
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Meeting Abstract number: 567

 
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Created: Tue, 02 Mar 2010, 11:06:22 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience