부산대학교 도서관

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. Author summary: Conventional post-translational modifications play essential roles in host antiviral immune response and viral immune evasion. Recently, a set of atypical acylations involving lysine propionylation (Kpr) have been discovered. However, whether Kpr modification occurs in viral proteins or regulates viral immune evasion remain unknown. Our study uncovers Kpr modification exists in viral interferon regulatory factor 1 (vIRF1) encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) to inhibit IFN-β production. 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. Thus, the current findings illustrate a novel mechanism of viral immune evasion strategies and provide a rationale for targeting of Kpr and the associated enzymes as an innovative therapeutic strategy of virus infections. [ABSTRACT FROM AUTHOR]