KAP1/TRIM28 – antiviral and proviral protagonist of herpesvirus biology.

Epigenetic silencing of lytic phase viral genes is central to the persistence of herpesviruses. The role of the transcriptional corepressor KAP1 in silencing both 'self' endogenous retroviral elements and foreign herpesvirus genomes is an evolving field. Apart from its antiviral role in maintaining latency, following disruption of latency, KAP1 propels the lytic phase by amplifying expression of lytic genes and enables transition from transcription to replication of herpesvirus genomes. Selective disruption of KAP1's dual roles in latency and lytic phases provides attractive approaches to thwart herpesvirus-related diseases that can arise from one or the other phase of the viral life cycle. Dysregulation of the constitutive heterochromatin machinery (HCM) that silences pericentromeric regions and endogenous retroviral elements in the human genome has consequences for aging and cancer. By recruiting epigenetic regulators, Krüppel-associated box (KRAB)-associated protein 1 (KAP1/TRIM28/TIF1β) is integral to the function of the HCM. Epigenetically silencing DNA genomes of incoming herpesviruses to enforce latency, KAP1 and HCM also serve in an antiviral capacity. In addition to gene silencing, newer reports highlight KAP1's ability to directly activate cellular gene transcription. Here, we discuss the many facets of KAP1, including recent findings that unexpectedly connect KAP1 to the inflammasome, reveal KAP1 cleavage as a novel mode of regulation, and argue for a pro-herpesviral KAP1 function that ensures transition from transcription to replication of the herpesvirus genome. [ABSTRACT FROM AUTHOR]