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DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing

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 sho...

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Autores principales: Scutts, Simon R., Ember, Stuart W., Ren, Hongwei, Ye, Chao, Lovejoy, Christopher A., Mazzon, Michela, Veyer, David L., Sumner, Rebecca P., Smith, Geoffrey L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250978/
https://www.ncbi.nlm.nih.gov/pubmed/30428360
http://dx.doi.org/10.1016/j.celrep.2018.10.034
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author Scutts, Simon R.
Ember, Stuart W.
Ren, Hongwei
Ye, Chao
Lovejoy, Christopher A.
Mazzon, Michela
Veyer, David L.
Sumner, Rebecca P.
Smith, Geoffrey L.
author_facet Scutts, Simon R.
Ember, Stuart W.
Ren, Hongwei
Ye, Chao
Lovejoy, Christopher A.
Mazzon, Michela
Veyer, David L.
Sumner, Rebecca P.
Smith, Geoffrey L.
author_sort Scutts, Simon R.
collection PubMed
description 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.
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spelling pubmed-62509782018-11-30 DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing Scutts, Simon R. Ember, Stuart W. Ren, Hongwei Ye, Chao Lovejoy, Christopher A. Mazzon, Michela Veyer, David L. Sumner, Rebecca P. Smith, Geoffrey L. Cell Rep Article 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. Cell Press 2018-11-13 /pmc/articles/PMC6250978/ /pubmed/30428360 http://dx.doi.org/10.1016/j.celrep.2018.10.034 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Scutts, Simon R.
Ember, Stuart W.
Ren, Hongwei
Ye, Chao
Lovejoy, Christopher A.
Mazzon, Michela
Veyer, David L.
Sumner, Rebecca P.
Smith, Geoffrey L.
DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250978/
https://www.ncbi.nlm.nih.gov/pubmed/30428360
http://dx.doi.org/10.1016/j.celrep.2018.10.034
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