title: A novel role of SIRT1 in gammaherpesvirus latency and replication.
abstract: Viruses often hijack cellular functions to facilitate their infection and replication. SIRT1, one of the most widely studied sirtuins, functions as both metabolic sensor and transcriptional regulator. SIRT1 has broad cellular functions including metabolic homeostasis, stress response, tumorigenesis and autophagy. The role of SIRT1 in the life cycle of viruses remains unclear. Like all herpesviruses, oncogenic gammaherpesvirus KSHV has both latent and lytic phases. In a recent study, we have shown that SIRT1 binds to the promoter and silence the expression of KSHV replication and transcription activator (RTA), a key activator of viral lytic replication. Chemical inhibition or knock down of SIRT1 is sufficient to initiate the lytic replication program by increasing active histone H3 trimethyl Lys4 (H3K4me3) mark and decreasing repressive histone H3 trimethyl Lys27 (H3K27me3) mark in the RTA promoter. SIRT1 also interacts with RTA and inhibits RTA transactivation of its own promoter and those of downstream target genes. Our findings reveal that SIRT1 regulates KSHV latency by inhibiting different stages of viral lytic replication, and link a metabolic sensor and transcriptional regulator SIRT1 to KSHV life cycle.
authors.affiliation: a Department of Molecular Microbiology and Immunology; Keck School of Medicine ; University of Southern California ; Los Angeles , CA , USA.
authors.forename: Meilan
authors.initials: M
authors.lastname: He
authors.forename: Shou-Jiang
authors.initials: SJ
authors.lastname: Gao
mesh_terms: D031204:Caloric Restriction; D002460:Cell Line; D004261:DNA Replication; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009243:NAD / Q000378:metabolism; D011401:Promoter Regions, Genetic; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency
chemical_list: D006657:Histones; D015534:Trans-Activators; D014764:Viral Proteins; D009243:NAD; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Epigenetics; H3K4me3 and H3K27me3; KSHV Latency and Reactivation; Kaposi's Sarcoma; Kaposi's Sarcoma-Associated Herpesvirus (KSHV); Metabolism; Nicotinamide; Primary effusion lymphoma; SIRT1