부산대학교 도서관

SUMO modifications regulate the function of many proteins and are important in controlling herpesvirus infections. We performed a site-specific proteomic analysis of SUMO1- and SUMO2-modified proteins in Epstein-Barr virus (EBV) latent and lytic infection to identify proteins that change in SUMO modification status in response to EBV reactivation. Major changes were identified in all three components of the TRIM24/TRIM28/TRIM33 complex, with TRIM24 being rapidly degraded and TRIM33 being phosphorylated and SUMOylated in response to EBV lytic infection. Further experiments revealed TRIM24 and TRIM33 repress expression of the EBV BZLF1 lytic switch gene, suppressing EBV reactivation. However, BZLF1 was shown to interact with TRIM24 and TRIM33, resulting in disruption of TRIM24/TRIM28/TRIM33 complexes, degradation of TRIM24 and modification followed by degradation of TRIM33. Therefore, we have identified TRIM24 and TRIM33 as cellular antiviral defence factors against EBV lytic infection and established the mechanism by which BZLF1 disables this defence. Author summary: The activity of many proteins is controlled by modification by the small ubiquitin-like modifier (SUMO), and some of these proteins are part of antiviral responses that limit herpesvirus infections, including Epstein-Barr virus (EBV). While often asymptomatic, EBV is clinically relevant as a causative agent in several types of cancer as well as multiple sclerosis. To identify regulators of EBV, we performed a large-scale analysis of SUMO-modified proteins that change in modification or abundance in response to reactivation of EBV from latent to lytic infection. Interesting findings include changes in three related proteins (TRIM24/TRIM28/TRIM33) known to form a complex. Further studies showed that these proteins inhibit EBV lytic infection by suppressing the expression of the first lytic protein, BZLF1. However, BZLF1 was found to interact with and destabilize TRIM24 and TRIM33, disabling their antiviral function. Therefore, we have identified a new cellular defense against EBV and a mechanism by which this virus disables the cellular response. [ABSTRACT FROM AUTHOR]