In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 4 ( 2023-4-6), p. e1011324-
Abstract:
Post-translational modifications (PTMs) are essential for host antiviral immune response and viral immune evasion. Among a set of novel acylations, lysine propionylation (Kpr) has been detected in both histone and non-histone proteins. However, whether protein propionylation occurs in any viral proteins and whether such modifications regulate viral immune evasion remain elusive. Here, we show that Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded viral interferon regulatory factor 1 (vIRF1) can be propionylated in lysine residues, which is required for effective inhibition of IFN-β production and antiviral signaling. Mechanistically, vIRF1 promotes its own propionylation by blocking SIRT6’s interaction with ubiquitin-specific peptidase 10 (USP10) leading to its degradation via a ubiquitin-proteasome pathway. Furthermore, vIRF1 propionylation is required for its function to block IRF3-CBP/p300 recruitment and repress the STING DNA sensing pathway. A SIRT6-specific activator, UBCS039, rescues propionylated vIRF1-mediated repression of IFN-β signaling. These results reveal a novel mechanism of viral evasion of innate immunity through propionylation of a viral protein. The findings suggest that enzymes involved in viral propionylation could be potential targets for preventing viral infections.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011324
DOI:
10.1371/journal.ppat.1011324.g001
DOI:
10.1371/journal.ppat.1011324.g002
DOI:
10.1371/journal.ppat.1011324.g003
DOI:
10.1371/journal.ppat.1011324.g004
DOI:
10.1371/journal.ppat.1011324.g005
DOI:
10.1371/journal.ppat.1011324.g006
DOI:
10.1371/journal.ppat.1011324.g007
DOI:
10.1371/journal.ppat.1011324.s001
DOI:
10.1371/journal.ppat.1011324.s002
DOI:
10.1371/journal.ppat.1011324.s003
DOI:
10.1371/journal.ppat.1011324.s004
DOI:
10.1371/journal.ppat.1011324.s005
DOI:
10.1371/journal.ppat.1011324.s006
DOI:
10.1371/journal.ppat.1011324.s007
DOI:
10.1371/journal.ppat.1011324.s008
DOI:
10.1371/journal.ppat.1011324.s009
DOI:
10.1371/journal.ppat.1011324.s010
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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