Project Reference: TRG27-PAT-CC1

Project title: Investigating conserved mechanisms of alphaherpesvirus evasion of intracellular immune defences.

Project outline

Alphaherpesviruses infect and cause disease in a wide range of mammals, birds and reptiles. These viruses usually infect a specific host-species where they establish lifelong infections, commonly in sensory neurons. Alphaherpesviruses can also spread to the central nervous system where they can cause viral encephalitis, and there is increasing evidence that alphaherpesvirus infections are important risk factors in the development of dementia. While rare, these viruses can also jump between species and cause zoonotic infections.

This project will be focused on how these viruses successfully evade intracellular antiviral responses. Alphaherpeseviruses have a broad range of mechanisms to antagonise antiviral responses, and we have recently discovered a novel complex of 3 viral proteins in herpes simplex virus-1 (HSV-1) that mediates the destruction of specific host antiviral proteins. This tripartite viral protein complex is conserved across diverse alphaherpesviruses.

The aims of this project are to understand the conservation and differences in the molecular functions and activity of this viral protein complex between human and equine viruses in an interdisciplinary project that bridges molecular virology and veterinary medicine with likely impacts on future vaccine design. 

Genetically modified HSV-1 and equine herpes virus-1 (EHV-1) strains will be generated to investigate protein localisation in infected cells (live cell imaging), cellular interaction partners (BioID) and inhibit specific functions of the viral complex. Advanced microscopy imaging, targeted host protein depletion (Degrons), and the use of human/equine epithelial, neuronal, and organotypic cultures will be used to investigate impacts on virus replication/spread, and host responses to infection.

This research will provide novel understanding of important viral pathogens helping the design of live attenuated vaccines, as well as cellular mechanisms involved with detecting and combating such viruses.

Principal Supervisor

Professor Colin Crump

Email address: cmc56@cam.ac.uk

Department / Partner Institute: Pathology

Website: https://www.path.cam.ac.uk/research/virology/crump-group

BBSRC strategic theme

Bioscience for an integrated understanding of health