Scutts, SR;
Ember, SW;
Ren, H;
Ye, C;
Lovejoy, CA;
Mazzon, M;
Veyer, DL;
... Smith, GL; + view all
(2018)
DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing.
Cell Reports
, 25
(7)
1953-1965.e4.
10.1016/j.celrep.2018.10.034.
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Abstract
Virus infection is sensed by pattern recognition receptors (PRRs) detecting virus nucleic acids and initiating an innate immune response. DNA-dependent protein kinase (DNA-PK) is a PRR that binds cytosolic DNA and is antagonized by vaccinia virus (VACV) protein C16. Here, VACV protein C4 is also shown to antagonize DNA-PK by binding to Ku and blocking Ku binding to DNA, leading to a reduced production of cytokines and chemokines in vivo and a diminished recruitment of inflammatory cells. C4 and C16 share redundancy in that a double deletion virus has reduced virulence not seen with single deletion viruses following intradermal infection. However, non-redundant functions exist because both single deletion viruses display attenuated virulence compared to wild-type VACV after intranasal infection. It is notable that VACV expresses two proteins to antagonize DNA-PK, but it is not known to target other DNA sensors, emphasizing the importance of this PRR in the response to infection in vivo.
| Type: | Article |
|---|---|
| Title: | DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2018.10.034 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2018.10.034 |
| Language: | English |
| Additional information: | Copyright © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | DNA sensing, DNA protein kinase, pattern recognition receptor, IRF3 signaling, vaccinia virus, immune evasion, protein C4, virulence factor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10081031 |
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