Characterising Tulavirus L protein and its interactome

As a result of the combined pressures of climate change, globalisation and increased land use, zoonotic diseases represent an increasing threat to global health. One important group of emerging zoonotic pathogens are Hantaviruses, widely distributed RNA viruses which mainly infect rodents and bats. 28 hantaviruses are known to infect humans, resulting in high mortality and morbidity haemorrhagic fevers. Hantaviruses are members of the larger Bunyavirus family, which includes multiple WHO-designated pathogens prioritised for research and development. Like all viruses, hantaviruses rely on the infection of their host's cells to reproduce and cause disease. To achieve this, they have evolved multifunctional proteins to subvert host processes and mediate the creation of new viral particles. Critically, these activities are often mediated through interactions with host proteins to stimulate host activities beneficial to the virus. Given the importance of hantaviruses and their relatives, investigating the host interactions of hantavirus proteins, as well as their structure, is therefore critical to understand the viral life cycle. Identification of viral interactions can additionally reveal the importance and role of human proteins, which were previously poorly understood. In my project, I will be using affinity and cross-linking Mass Spectrometry to identify these interactions in the hantavirus Tula virus, with a specific focus on the interactions of the viral L protein. The L protein is required for both the replication of the viral genome and the production of viral proteins and is therefore critical for infection. I will then employ a range of techniques to validate and explore these interactions to understand their importance in the viral life cycle. Finally, I additionally plan to investigate the structure and activity of the L protein directly using Cryo-electron microscopy.