Structural studies on human viruses

We wish to understand the structure of virus particles and how they interact with the host cell. This can provide insights into many aspects of virus biology and may suggest strategies for treatment. The Main virus being studied is herpes simplex virus, which is a widespread human pathogen causing a variety of diseases. Virus replication and virus particle formation are complex, multistage processes involving the products of many virus genes. We are determining the three-dimensional structure of the virus at different stages during its replication cycle to determine how the structure dictates the assembly and disassembly mechanisms. This is combined with molecular genetic analyses to produce a comprehensive description of the processes leading to the formation and spread of infectious virus particles.

Knowledge of the structure of viruses and how they interact with the host cell is essential for understanding the processes involved in infection. Virion morphogenesis is a central feature of the life cycle of any virus, and a clear understanding of this process can provide insights into many aspects of virus biology and may suggest possible strategies for therapeutic intervention. We use both structural and molecular genetic approaches to visualise virus particles at various stages during their replication. Herpesviruses are double-stranded DNA viruses that have icosahedral particles, which are surrounded by asymmetrical protein and lipid layers. The structure of the herpesvirus virion is under study in collaboration with Wah Chiu at Baylor College of Medicine in Houston. Both icosahedral and tomographic reconstruction approaches are being used to visualise the symmetrical and asymmetrical features of the particles and uncover the relationships between them. These structural analyses are now being extended to examine virus particles interacting with host cells at various stages during entry, transport and assembly. In parallel studies, the functions of virus structural proteins and their interactions with cellular proteins during the processes of infection and virus maturation, are being examined by molecular biological, mutational and microscopical studies. These complementary analyses are helping to produce fundamental insights into the processes controlling the assembly and dis-assembly, of these important pathogens.