St dynamics and transmission in laboratory studies [14,15]. Current theoretical and experimental evidence suggests that persistence within the atmosphere is definitely an significant aspect of transmission for avian influenza [164]. Transmission via an environmental stage (e.g. long-lasting droplets, fomites) seems to also play a part for influenza transmission in humans [259]. Because temperatures in the atmosphere and inside a host might be markedly diverse, it is actually feasible that the virus faces a trade-off: It can either optimize its potential to persist within a host, or optimizeModeling MedChemExpress BI-9564 temperature-dependent Influenza FitnessAuthor SummaryIt has lately been recommended that for avian influenza viruses, prolonged persistence within the atmosphere plays a vital role within the transmission amongst birds. In such circumstances, influenza virus strains might face a trade-off: they will need to persist well in the atmosphere at low temperatures, but they also need to have to complete nicely inside an infected bird at larger temperatures. Here, we analyze how possible trade-offs on these two scales interact to establish all round fitness with the virus. We find that the hyperlink between infection dynamics within PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20160000 a host and virus shedding and transmission is important in determining the relative advantage of fantastic low-temperature versus high-temperature persistence. We also find that the part of virus-induced mortality, the immune response and the route of transmission have an effect on the balance among optimal low-temperature and hightemperature persistence. its ability to persist outside a host. It can be well known that the decay rate of most viruses depends upon temperature, with faster virion decay occurring at larger temperature [302]. Interestingly, current information [33] recommend that temperature-dependent decay rates differ among influenza strains. Some strains are extremely steady at environmental temperatures ( 5{200 C) but rapidly decay at higher within-host temperatures ( 35{400 C), while others persist less well at low temperatures but also have a less rapid decay as temperature increases [33]. These data suggest that some virus strains might optimize persistence within a host, while others might optimize persistence outside a host, with a possible trade-off between the two. This in turn can affect both within-host and between-host dynamics. The dynamics on these two levels interact to determine overall fitness. (Note that the data presented in [33] which we will analyze below is for different HA-NA serotypes. However, the phenomenon of temperature-dependent decay we discuss is not specific to distinct serotypes. We will therefore use the generic term “strain” throughout this study). To analyze the impact that such a temperature-dependent trade-off can have on virus fitness, we build a multi-scale model that embeds a within-host infection process within a population transmission framework. A number of theoretical studies have previously considered trade-offs between environmental persistence and within-host performance, see e.g. [348]. Those studies considered generic trade-offs and models without direct relation to a specific pathogen or fitting to data. A few notable studies that involved data looked at environmental survival and virulence of human pathogens [39] and environmental survival and growth in phages [40]. Here, we focus on avian influenza A and combine experimental data with models to explicitly consider temperature-dependent virus decay as the mediator of trade-offs. We find that for di.