Geometry as a key to the virosphere: Mathematics as a driver of discovery in virology and anti-viral therapy

Professor Reidun Twarock, University of York

Viruses encapsulate their genetic material into protein containers that act akin to molecular Trojan horses, protecting viral genomes between rounds of infection and facilitating their release into the host cell environment. In the majority of viruses, including major human pathogens, these containers have icosahedral symmetry. Mathematical techniques from group, graph and tiling theory can therefore be used to better understand how viruses form, evolve and infect their hosts, and point the way to novel antiviral solutions.  In this talk, I will present an overarching theory of virus architecture, that contains the seminal Caspar Klug theory as a special case and solves long-standing open problems in structural virology. I will also introduce mathematical models of symmetry breaking in viral capids and discuss their consequences for our understanding of more complex capsid geometries.  Combining insights into virus structure with a range of different mathematical modelling techniques, such as Gillespie algorithms, I will show how viral life cycles can be better understood thorough the lens of viral geometry. In particular, I will demonstrate the instrumental role of the Hamiltonian path concept in the discovery of a virus assembly mechanism that occurs in many human pathogens, such as Picornaviruses – a family that includes the common cold virus – and Hepatitis B and C virus. I will use multi-scale models of a viral infection and implicit fitness landscapes in order to demonstrate that therapeutic interventions directed against this mechanism have advantages over conventional forms of anti-viral therapy. The talk will finish with a discussion of how the new mathematical and mechanistic insights can be exploited in bio-nanotechnology for applications in vaccination and gene therapy.