RESUMO
Animal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host's infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.
Assuntos
Coinfecção/virologia , Aptidão Genética , Virus da Influenza A Subtipo H5N1/genética , Infecções por Orthomyxoviridae/virologia , Animais , Evolução Molecular , Furões , Frequência do Gene , Humanos , Modelos Genéticos , MutaçãoRESUMO
Anthropogenic resource supplementation can shape wildlife disease directly by altering the traits and densities of hosts and parasites or indirectly by stimulating prey, competitor or predator species. We first assess the direct epidemiological consequences of supplementation, highlighting the similarities and differences between food provisioning and two widespread forms of nutrient input: agricultural fertilization and aquatic nutrient enrichment. We then review an aquatic disease system and a general model to assess whether predator and competitor species can enhance or overturn the direct effects of enrichment. All forms of supplementation can directly affect epidemics by increasing host population size or altering parasite production within hosts, but food provisioning is most likely to aggregate hosts and increase parasite transmission. However, if predators or competitors increase in response to supplementation, they could alter resource-fuelled outbreaks in focal hosts. We recommend identifying the traits of hosts, parasites or interacting species that best predict epidemiological responses to supplementation and evaluating the relative importance of these direct and indirect mechanisms. Theory and experiments should examine the timing of behavioural, physiological and demographic changes for realistic, variable scenarios of supplementation. A more integrative view of resource supplementation and wildlife disease could yield broadly applicable disease management strategies.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.
Assuntos
Daphnia/microbiologia , Doenças dos Peixes/epidemiologia , Interações Hospedeiro-Patógeno , Modelos Estatísticos , Micoses/veterinária , Animais , Clorófitas/microbiologia , Comportamento Competitivo/fisiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/transmissão , Peixes/microbiologia , Peixes/fisiologia , Cadeia Alimentar , Humanos , Metschnikowia/crescimento & desenvolvimento , Metschnikowia/patogenicidade , Micoses/epidemiologia , Micoses/microbiologia , Micoses/transmissão , Comportamento Predatório/fisiologia , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/patogenicidadeRESUMO
Selective sweeps reduce neutral genetic diversity. In sexual populations, this "hitchhiking" effect is thought to be limited to the local genomic region of the sweeping allele. While this is true in panmictic populations, we find that in spatially extended populations the combined effects of many unlinked sweeps can affect patterns of ancestry (and therefore neutral genetic diversity) across the whole genome. Even low rates of sweeps can be enough to skew the spatial locations of ancestors such that neutral mutations that occur in an individual living outside a small region in the center of the range have virtually no chance of fixing in the population. The fact that nearly all ancestry rapidly traces back to a small spatial region also means that relatedness between individuals falls off very slowly as a function of the spatial distance between them.