Antoni Wrobel
Wellcome Trust Career Development Fellow
Molecular mechanisms underlying viral evolution and host changes
Molecular mechanisms underlying viral evolution and host changes
Many deadly human pathogens, such as influenza and SARS viruses, are made up of relatively few components but can infect a number of different hosts. How is it possible that these components suffice to fulfil all the functions necessary for a virus to infect the cell and then to assemble into a new viral particle? How do viral proteins perform multiple functions and how does the virus manage to retain all these functions as it evolves? How does a virus infect different hosts using the same set of its own proteins to engage a range of machineries of different hosts? And, finally, how does a virus evolve and ‘learn’ to optimise its interactions with a new host?
The recent COVID-19 pandemic has demonstrated that these questions are key to understand where new viruses come from and how they evolve upon transmitting to a new host. We have used biochemical, biophysical, and structural methodologies, mainly cryoEM, to reveal the mechanisms by which SARS-CoV-2 became able to infect humans and then further evolved to optimise viral infectivity in the variants of concern. The lab continues to work on coronaviruses and studies influenza viruses to understand how their proteins achieve the versatility needed to infect diverse hosts and fulfil multiple functions during infection. In particular, we want to explain how related viral strains use similar glycoproteins to engage receptors as different as glycans and proteins. We are also interested in understanding how viruses assemble: how do viral components find themselves in the dense environment of the cell and how do cellular machineries facilitate and interfere with this process.
Tackling these questions can directly impact public health. The more we understand the rules governing the evolution of viral proteins, the better we can predict the impact of emerging viruses and thus increase our pandemic preparedness. Our long-term aim is to use structural and mechanistic insights to guide design of much-needed new antivirals and vaccines against zoonotic viruses.