DNA-PKcs is required for cGAS/STING-dependent viral DNA sensing in human cells.
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Embargo End Date
ICR Authors
Authors
Hristova, DB
Oliveira, M
Wagner, E
Melcher, A
Harrington, KJ
Belot, A
Ferguson, BJ
Oliveira, M
Wagner, E
Melcher, A
Harrington, KJ
Belot, A
Ferguson, BJ
Document Type
Journal Article
Date
2024-01-19
Date Accepted
2023-12-13
Abstract
To mount an efficient interferon response to virus infection, intracellular pattern recognition receptors (PRRs) sense viral nucleic acids and activate anti-viral gene transcription. The mechanisms by which intracellular DNA and DNA viruses are sensed are relevant not only to anti-viral innate immunity, but also to autoinflammation and anti-tumour immunity through the initiation of sterile inflammation by self-DNA recognition. The PRRs that directly sense and respond to viral or damaged self-DNA function by signaling to activate interferon regulatory factor (IRF)-dependent type one interferon (IFN-I) transcription. We and others have previously defined DNA-dependent protein kinase (DNA-PK) as an essential component of the DNA-dependent anti-viral innate immune system. Here, we show that DNA-PK is essential for cyclic GMP-AMP synthase (cGAS)- and stimulator of interferon genes (STING)-dependent IFN-I responses in human cells during stimulation with exogenous DNA and infection with DNA viruses.
Citation
iScience, 2024, 27 (1), pp. 108760 -
Source Title
iScience
Publisher
CELL PRESS
ISSN
2589-0042
eISSN
2589-0042
2589-0042
2589-0042
Collections
Research Team
Targeted Therapy