Colin McVey Lab

	We are studying the mechanisms involved in the establishment and modulation of herpesviral chromatin. Chromatin modulation is a key process that governs the infectious or persistent cycle of herpesviruses. The long-term goal is to understand how these processes contribute to virus tumourigenesis.
	Colin E. McVey Principal Investigator PhD in Chemistry, University of York, UK Phone (+351) 214469663 | Extension 1663 Email mcvey@itqb.unl.pt | Lab webpage

Research Interests

Our research is focused on Kaposi’s sarcoma-associated herpesvirus (KSHV) epigenome and the proteins encoded by the virus to understand their role in viral latency. Viral latency is the ability of a pathogenic virus to lie dormant within a cell. We focus on LANA, a viral protein that binds to the viral DNA and is central for viral latency.

We are interested in understanding the mechanisms involved in the establishment and modulation of herpesviral chromatin by LANA:

1. chromatin modulation governs the infectious or persistent cycle of herpesviruses;
2. the viral epigenome is a microcosm of the cell genome, and important insights into chromatin modification can be discovered from viral modulation;
3. the herpesvirus LANA protein interacts with host chromatin modifiers to regulate the cellular chromatin machinery

LANA recruits heterochromatin components to the viral genome to establish latent infection. LANA orchestrates interactions with host chromatin modifiers to regulate the cellular chromatin machinery to maintain the viral epigenome. The McVey lab combines both biophysical and structural methods to understand the protein interactions involved in chromatin modulation by LANA.

Establishment and maintenance of viral epigenome

Ongoing projects:

• Structural basis of Viral DNA binding by LANA
• Mechanism of DNA cooperative binding and oligomerization by LANA
• Characterization of LANA chromatin modifier complexes

Group Members

Collaborations

• Marta Pires de Miranda (Institute of Molecular Medicine, Lisbon, PT)
• Kenneth Kaye (Harvard Medical School, USA)
• Pedro Simas (Institute of Molecular Medicine, Lisbon, PT)

Selected Publications 

1. Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA: PLoS Pathogens 2017

2. KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA: Nucleic Acids Research 2015

3. Crystal Structure of the Gamma-2 Herpesvirus LANA DNA Binding Domain Identifies Charged Surface Residues Which Impact Viral Latency: PLoS Pathogens 2013

4. MLL1 is regulated by KSHV LANA and is important for virus latency: Nucleic Acids Research 2021

Laboratory's Website

For further information please visit the Laboratory's Website

Virologia Estrutural (PT)

Unidade de Cristalografia de Macromoléculas

A nossa investigação foca-se no estudo dos mecanismos envolvidos no estabelecimento de latência e modulação da cromatina herpesviral. A modulação da cromatina é um processo fundamental que governa o ciclo infeccioso ou persistente dos vírus do herpes. O objetivo a longo prazo é entender como esses processos contribuem para a tumorigénese do vírus Herpes.

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