Viruses must evade multiple host immune defences throughout infection in order to promote their replication and spread. This programme of research aims to identify and define key viral host-cell interactions that influence the regulation of intracellular host immunity during virus infection.
There are eight herpesviruses (HHV 1-8) that are endemic within the human population. Whilst primary infection can often result in mild or asymptomatic illness, herpesviruses are the principal causative agents associated with a number of severe and potentially life-threatening diseases. A common feature shared by all herpesviruses is their ability to establish a life-long latent infection within their host, which can periodically undergo episodes of viral reactivation leading to recurrent disease and transmission.
Antivirals (acyclovir, valacyclovir, and famciclovir) are effective at limiting viral spread, but do not inhibit viral reactivation from latency and carry health risks with prolonged use. Understanding the molecular mechanisms that regulated the balance between lytic (active) and latent (silent) states of infection remains an important area of research that may provide novel avenues in the development of new or alternative antiviral therapies.
The post-translational modification (PTM) of proteins by ubiquitin and ubiquitin-like (UBL) modifiers regulates many important aspects of cell biology including multiple facets relating to host immunity during pathogenic infection. Many viruses have evolved strategies to utilise or suppress these PTM pathways in order to enhance their replication and spread. However, whilst it is clear that these pathways play a pivotal role in the regulation of viral infection, the biochemistry of these interactions remain largely undefined.
By defining the biochemistry of these interactions we aim to:
- Significantly advance our current understanding as to the biochemical mechanisms that regulate intrinsic and innate immunity during DNA virus infection
- Develop novel methodologies for the future screening and identification of compounds that restrict herpesvirus replication and pathogenesis
Collaborators: Ben Hale, University of Zurich; Peter Mertens & Sue Jacobs, The Pirbright Institute; David Davido, University of Kansas; Patrick Lomonte, Université Claude Bernard Lyon;
Research interests: Many human viruses utilise or suppress ubiquitin and ubiquitin-like pathways during infection, enhancing their replication. I'm interested in how viruses engage with these pathways with respect to cellular antiviral immunity, to develop novel avenues for therapeutic intervention.
Research interests: We investigate the control of herpes simplex virus type 1 (HSV-1) gene expression during productive & quiescent infection. We focus on the viral and cellular factors that regulate the initial stages of lytic infection, and the potential involvement of these factors during latency.