Viruses with RNA genomes like dengue, Zika, polio and vesicular stomatitis virus have the potential to evolve rapidly, over similar timescales to transmission, due to the lack of a proof-reading polymerase. In addition to replication errors due to low fidelity, for some viruses, their intracellular replication strategy also increases mutation rates. Therefore, there is potential for selection to occur at both the within and between-cell levels.

Although a large body of theoretical work has focussed on the evolutionary dynamics of phage at the between-cell level, fewer studies have focussed on the evolutionary dynamics of RNA viruses of protozoa and animals at these small scales. Advances in single-cell virology are enabling the study of within-cell dynamics of viruses, but models of within cell dynamics and, particularly, those linking within and between cell virus replication are scant. 

Virions cannot be immediately released from infected cells; they must go through six steps before mature virions are produced. The strategy a virus takes through these steps influences the mutation rate, virus yield, the time to infection of new cells and potentially the cell death rate.

All these factors influence between-cell transmission dynamics and trade-offs between them may influence virus evolution. For example, an increase in replication rate may lead to earlier cell death. Viruses of protozoa and animals are capable of exiting cells either by keeping the host cell alive and budding from the cell membrane, or inducing apoptosis and releasing virions during cell death. Using a mathematical model of between-cell transmission, we have recently shown that fitness minima exist at this level with respect to the time it takes for virus to kill the cell, when either virus can exit by budding or by killing the host cell. This means that intermediate times to apoptosis lead to virus fitness that is lower than short times to apoptosis; leading to an apoptotic strategy, and long times to apoptosis; leading to a budding strategy.

Collaborators: Dr Jennifer Lord, LSTM.

Selected publications

Lord, J.S and M.B. Bonsall (2021) The evolutionary dynamics of viruses: virion release strategies, time delays and fitness minima. Virus Evolution 7, veab039. https://doi.org/10.1093/ve/veab039