Mathematical Virology: The Impact of Virus Structure and Function on Viral Evolution

Society faces a number of major challenges due to the impact of global warming on world climate. One consequence is the spread of otherwise rare and poorly characterised viral infections into economically advanced areas of the world. Examples include Bluetongue virus, which arrived in the UK after years of being restricted to much warmer climates. This poses a threat to public and animal health from both existing viruses and newly emerging ones.
A major problem in the design of anti-viral therapies is the emergence of viral strains that are resistant to anti-viral drugs soon after initial treatment. Research into the mechanisms that could prevent such viral escape mutants is therefore urgently required in order to develop therapeutics with long-term action. Moreover, viruses can evolve strains that cross the species barrier, for example from an animal to a human host as in the case of bird flu, and it is important to be able to develop strategies to prevent this. Insights into virus evolution could shed light on both issues. In particular, we need to better understand the constraints that viruses face when their genomes evolve, and find ways of predicting such evolutionary behaviour.
In previous research we have gained fundamentally new insights into the constraints underlying virus structure and function, and we investigate here their impact on the evolution of viruses. If we improve our understanding of the factors that determine the evolutionary behaviour of viruses, we will be able to explore strategies to misdirect viral evolution. In particular, this analysis will allow us to quantify in how far the structural constraints we have discovered earlier lead to evolutionary bottlenecks, i.e. correspond to constraints that the viral escape mutants cannot avoid, and that a new generation of anti-viral therapeutics could target. Moreover, we plan to develop methods to predict how viruses may react to a drug, and use this to test the impact of different anti-viral strategies. This research has the potential to lead to a new generation of "evolutionarily-stable" therapeutics that are less susceptible to the problem of escape mutants.

Society faces a number of major challenges due to the impact of global warming on world climate. One consequence is the spread of otherwise rare and poorly characterised viral infections into economically advanced areas of the world. Examples include Bluetongue virus, which arrived in the UK after years of being restricted to much warmer climates. This poses a threat to public and animal health from both existing viruses and newly emerging ones.
A major problem in the design of anti-viral therapies is the emergence of resistant viral strains that arise soon after being challenged by a drug or the immune system. Research into the mechanisms that could prevent such viral escape is therefore urgently required. Moreover, viruses can evolve strains that cross the species barrier, for example from an animal to a human host as in the case of bird flu. Both issues can be addressed via an analysis of the evolutionary behaviour of viruses. In particular, we need to better understand the selective pressures and constraints that impact on viral evolution, and find ways of predicting the evolutionary behaviour of viruses.
In previous research we have gained fundamental new insights into the constraints underlying virus structure and function, and we investigate here their impact on the evolution of viruses. If we improve our understanding of the factors that determine the evolutionary behaviour of viruses, we will be able to explore strategies to misdirect viral evolution. In particular, this analysis will allow us to quantify in how far these structural constraints lead to evolutionary bottlenecks that viral escape mutants encounter, and that a new generation of anti-viral therapeutics could endeavour to block. Moreover, if we develop methods to predict how viruses may react to a drug, we can also test the impact of other anti-viral strategies.
The long-term impact of this research on the public health sector may be significant, because the research direction that is initiated with this feasibility study has the potential to lead to a new generation of "evolutionarily-stable" anti-viral therapeutics.