A Multi-scale Analysis of Influenza A Virus Fitness Trade-offs due to Temperature-dependent Virus Persistence

Abstract

Successful replication within an infected host and successful transmission between hosts are key to the continued spread of most pathogens. Competing selection pressures exerted at these different scales can lead to evolutionary trade-offs between the determinants of fitness within and between hosts. Here, we examine such a trade-off in the context of influenza A viruses and the differential pressures exerted by temperature-dependent virus persistence. For a panel of avian influenza A virus strains, we find evidence for a trade-off between the persistence at high versus low temperatures. Combining a within-host model of influenza infection dynamics with a between-host transmission model, we study how such a trade-off affects virus fitness on the host population level. We show that conclusions regarding overall fitness are affected by the type of link assumed between the within- and between-host levels and the main route of transmission (direct or environmental). The relative importance of virulence and immune response mediated virus clearance are also found to influence the fitness impacts of virus persistence at low versus high temperatures. Based on our results, we predict that if transmission occurs mainly directly and scales linearly with virus load, and virulence or immune responses are negligible, the evolutionary pressure for influenza viruses to evolve toward good persistence at high within-host temperatures dominates. For all other scenarios, influenza viruses with good environmental persistence at low temperatures seem to be favored.

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

“…As previously found, there is a negative linear correlation for both log(a) versus log(g) and the relative ranks of a and g. The trade-off exists independent of the assumption about the error structure made when fitting the data. The combination of results in figure 5 and those previously reported in [31] suggests strongly that there is indeed a trade-off for virus decay at different temperatures, with some strains optimizing persistence at low temperatures, while others fare relatively better at high temperatures.…”

“…We find-perhaps surprisingly-little evidence for a trade-off of this phenotype between the environmental and the withinhost scales. Instead, confirming findings from a previous study [31], we find that a temperature-dependent trade-off exists on a single scale, namely the environmental stage.…”

“…The limit of detection for the virus load was 2.07 EID 50 (EID 50 ¼ median embryo infectious dose). For the mechanistic model, we set the initial number of uninfected target cells to 2.5 Â 10 7 as done previously [31,40].…”

“…To our knowledge, while multi-scale trade-offs in influenza A viruses have been postulated [31], no direct evidence of their existence has been presented. Here, we combine mathematical models with a unique dataset of viral load dynamics following influenza infections in ducks and viral persistence in water to analyse the temperature-dependent persistence phenotype and to study whether this phenotype encounters any trade-offs.…”

Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge

“…Some studies have considered transmission to be linked to the instantaneous viral load [27,28], whereas others have instead explored the total area under the curve (AUC) [29][30][31]. Among those models assuming transmission to scale with total virus load (AUC), alternative assumptions include transmission scaling with viral load on a logarithmic scale [16,32] or through a linear relationship [16].…”