In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-10), p. e1009901-
Abstract:
Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009901
DOI:
10.1371/journal.ppat.1009901.g001
DOI:
10.1371/journal.ppat.1009901.g002
DOI:
10.1371/journal.ppat.1009901.g003
DOI:
10.1371/journal.ppat.1009901.g004
DOI:
10.1371/journal.ppat.1009901.g005
DOI:
10.1371/journal.ppat.1009901.g006
DOI:
10.1371/journal.ppat.1009901.g007
DOI:
10.1371/journal.ppat.1009901.s001
DOI:
10.1371/journal.ppat.1009901.s002
DOI:
10.1371/journal.ppat.1009901.s003
DOI:
10.1371/journal.ppat.1009901.s004
DOI:
10.1371/journal.ppat.1009901.s005
DOI:
10.1371/journal.ppat.1009901.s006
DOI:
10.1371/journal.ppat.1009901.s007
DOI:
10.1371/journal.ppat.1009901.s008
DOI:
10.1371/journal.ppat.1009901.s009
DOI:
10.1371/journal.ppat.1009901.s010
DOI:
10.1371/journal.ppat.1009901.s011
DOI:
10.1371/journal.ppat.1009901.s012
DOI:
10.1371/journal.ppat.1009901.s013
DOI:
10.1371/journal.ppat.1009901.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
