[SCAN] KSHV LANA – A Chromatin Modulator

Title: KSHV LANA – A Chromatin Modulator

Speaker: Colin McVey

Abstract: Like other herpesviruses, KSHV establishes persistent infection which alternates between latent and lytic phases of replication. Latent infection predominates in KSHV infected tumour cells in which the linear viral genome undergoes circularization and chromatization. Key to KSHV survival in humans is the viral nuclear protein, LANA. LANA is essential for latency and is expressed in all KSHV infected tumours. LANA is a DNA binding protein and localizes to multiple terminal repeat (TR) DNA sites on the viral epigenome that assemble to form specific dot structures. LANA foci in KSHV-infected cells recruit heterochromatin components to the viral genome, which may lead to the establishment of viral latency and govern the transcription program.

Viral genomes need chromatin for protection and to execute their gene expression programs correctly. Viral chromatin is subject to histone modifications, “viral epigenetic marks”, which controls viral gene expression and replication. LANA binds to the terminal repeat (TR) DNA region of the KSHV genome. TR binding is thought to influence the chromatin organization of the viral episome through recruitment of chromatin-regulatory proteins like methyltransferase (KMT) and deubiquitinase (DUB) responsible for histone H3 lysine methylation and histone H2B deubiquitination, respectively. Dysregulation of both Histone ubiquitination and methylation has been associated with several pathological processes, particularly cancer.

In this seminar, I will present biophysical studies and the X-ray structure of LANA peptide motifs complexed with components of chromatin modifier complexes. This reveals a potential regulatory mechanism for chromatin methylation by DNA viruses.

 

ITQB NOVA Virtual Auditorium

Join the session: https://zoom.us/j/93139069443