K-bZIP Mediated SUMO-2/3 Specific Modification on the KSHV Genome Negatively Regulates Lytic Gene Expression and Viral Reactivation

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Establishment of KSHV persistent infection requires a dynamic balance between latency, a phase where most viral genes are silenced, and lytic cycle, a phase when nearly all viral genes are expressed. Disruption of this balance may augment virus clearance. During the latent-to-lytic switch, KSHV genomes are subjected to profound epigenetic changes. SUMOylation promotes targeting of proteins to different DNA sites, thereby helping to create specific epigenetic patterns that switch genes between active and inactive stages. It comes as no surprise that SUMOylation may be involved in chromatin remodeling of the KSHV genome during the latent-to-lytic switch and SUMOylation inhibition may disrupt the balance between KSHV latent and lytic cycle. In this study, we identified a profound SUMO-2/3 enrichment in KSHV genome euchromatin regions upon reactivation. SUMO-2/3 modification is responsible for diminishing viral gene expression after reactivation. KSHV SUMO-2/3-specific E3 ligase K-bZIP mediates the SUMO-2/3 enrichment during reactivation. Loss of E3 ligase activity of K-bZIP in the viral context increases viral lytic gene expression and virus production. Our findings demonstrate, for the first time, a SUMO-2/3-specific modification affecting transcription which regulates viral lytic gene expression, and uncovers a novel therapeutic strategy to disrupt persistent infection.

Vyšlo v časopise: K-bZIP Mediated SUMO-2/3 Specific Modification on the KSHV Genome Negatively Regulates Lytic Gene Expression and Viral Reactivation. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005051
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005051

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