Investigations into Vaccinia virus pathogenesis

This PhD project will investigate the mechanisms the poxvirus Vaccinia virus uses to replicate in a host cell. Our laboratory has carried out a high throughput screen of potential host factors that influence Vaccinia virus (VV) replication, identifying novel cellular proteins which act as susceptibility or resistance factors to the virus. This PhD project will investigate the mechanism of function of high priority candidates.

Background to Vaccinia virus
Vaccinia virus was most famously used in the 19th and 20th centuries as a very successful vaccine against smallpox (which is caused by the closely related poxvirus Variola virus), leading to the worldwide eradication of this disease in 1980. VV has also been used as a model for poxviral disease and a tool for investigating cellular biological mechanisms such as actin regulation and antiviral immune responses. VV is well suited to investigating cell biology mechanisms because there are well characterised methods for generating viral mutants and excellent animal models of poxviral disease.

VV is a large virus, encoding over 200 proteins from its large double-stranded DNA genome which enables it to undertake a particularly complicated cytoplasmic life cycle. One of the most elaborate areas of poxvirus biology is their numerous and varied immune avoidance strategies.

Project summary
This project will investigate relatively poorly characterised susceptibility or resistance factors identified in the high throughput screen which are believed to influence the innate immune system. The student will carry out mechanistic studies to identify how the proteins affect viral replication and immune signalling.

Anticipated project outcomes:
The knowledge gained from this PhD project will add to our knowledge of poxvirus pathogenesis and elucidate basic cellular mechanisms. It may be applied to the improvement of poxvirus-based vaccine vectors.