DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing
Summary: 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718316103 |
| _version_ | 1818910839574364160 |
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| author | Simon R. Scutts Stuart W. Ember Hongwei Ren Chao Ye Christopher A. Lovejoy Michela Mazzon David L. Veyer Rebecca P. Sumner Geoffrey L. Smith |
| author_facet | Simon R. Scutts Stuart W. Ember Hongwei Ren Chao Ye Christopher A. Lovejoy Michela Mazzon David L. Veyer Rebecca P. Sumner Geoffrey L. Smith |
| author_sort | Simon R. Scutts |
| collection | DOAJ |
| description | Summary: 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. : DNA-PK is a pattern recognition receptor (PRR) that binds cytosolic DNA and stimulates IRF3 signaling. Scutts et al. show that vaccinia virus antagonizes this DNA sensor with two proteins, C4 and C16, which both block DNA binding. Keywords: DNA sensing, DNA protein kinase, pattern recognition receptor, IRF3 signaling, vaccinia virus, immune evasion, protein C4, virulence factor |
| first_indexed | 2024-12-19T22:49:11Z |
| format | Article |
| id | doaj.art-2e9af660b028485482172474468ea970 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T22:49:11Z |
| publishDate | 2018-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2e9af660b028485482172474468ea9702022-12-21T20:02:52ZengElsevierCell Reports2211-12472018-11-0125719531965.e4DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA SensingSimon R. Scutts0Stuart W. Ember1Hongwei Ren2Chao Ye3Christopher A. Lovejoy4Michela Mazzon5David L. Veyer6Rebecca P. Sumner7Geoffrey L. Smith8Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Corresponding authorSummary: 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. : DNA-PK is a pattern recognition receptor (PRR) that binds cytosolic DNA and stimulates IRF3 signaling. Scutts et al. show that vaccinia virus antagonizes this DNA sensor with two proteins, C4 and C16, which both block DNA binding. Keywords: DNA sensing, DNA protein kinase, pattern recognition receptor, IRF3 signaling, vaccinia virus, immune evasion, protein C4, virulence factorhttp://www.sciencedirect.com/science/article/pii/S2211124718316103 |
| spellingShingle | Simon R. Scutts Stuart W. Ember Hongwei Ren Chao Ye Christopher A. Lovejoy Michela Mazzon David L. Veyer Rebecca P. Sumner Geoffrey L. Smith DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing Cell Reports |
| title | DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing |
| title_full | DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing |
| title_fullStr | DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing |
| title_full_unstemmed | DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing |
| title_short | DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing |
| title_sort | dna pk is targeted by multiple vaccinia virus proteins to inhibit dna sensing |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718316103 |
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