Professor Tony Minson & Dr Helena Browne
Herpesviruses are among the largest and most complex viruses. Different members of the family are responsible for a wide range of human diseases, such as chicken pox, glandular fever, cold sores and genital herpes, as well as economically important infections in domestic animals. All herpesviruses are composed of at least 30 different proteins of which ten or more are integral membrane proteins, embedded in the lipid bilayer of 'envelope' which surrounds the virus particle. Interactions between these membrane proteins and the surface or the host cell form the first step in the infection process, inducing fusion of the virus and host membranes and releasing the virus core into the cell. This ability to induce membrane fusion is a feature of all enveloped viruses but herpesviruses are unusual in that the concerted action of four different viral membrane proteins is required to achieve fusion and virus entry into the host cell. Our research attempts to define how the integral membrane proteins are assembled into the virus particle, and how they function in concert to promote membrane fusion.
Our approaches include:
- The construction of site-directed mutant glycoproteins and the use of these mutant molecules in membrane fusion and virus entry assays.
- Searches for host cell receptors to which virion membrane proteins bind.
- Immuno-EM analysis of the trafficking of viral glycoproteins.
- Production of purified membrane proteins for structural analysis.
- Analysis of the effect of virus binding on intracellular signalling pathways.