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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Scutts SR,Ember SW,Ren H,Ye C,Lovejoy CA,Mazzon M,Veyer DL,Sumner RP,Smith GL

doi

10.1016/j.celrep.2018.10.034

subject

Has Abstract

pub_date

2018-11-13 00:00:00

pages

1953-1965.e4

issue

7

issn

2211-1247

pii

S2211-1247(18)31610-3

journal_volume

25

pub_type

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