74 research outputs found
Strength and tempo of selection revealed in viral gene genealogies
Abstract
Background
RNA viruses evolve extremely quickly, allowing them to rapidly adapt to new environmental conditions. Viral pathogens, such as influenza virus, exploit this capacity for evolutionary change to persist within the human population despite substantial immune pressure. Understanding the process of adaptation in these viral systems is essential to our efforts to combat infectious disease.
Results
Through analysis of simulated populations and sequence data from influenza A (H3N2) and measles virus, we show how phylogenetic and population genetic techniques can be used to assess the strength and temporal pattern of adaptive evolution. The action of natural selection affects the shape of the genealogical tree connecting members of an evolving population, causing deviations from the neutral expectation. The magnitude and distribution of these deviations lends insight into the historical pattern of evolution and adaptation in the viral population. We quantify the degree of ongoing adaptation in influenza and measles virus through comparison of census population size and effective population size inferred from genealogical patterns, finding a 60-fold greater deviation in influenza than in measles. We also examine the tempo of adaptation in influenza, finding evidence for both continuous and episodic change.
Conclusions
Our results have important consequences for understanding the epidemiological and evolutionary dynamics of the influenza virus. Additionally, these general techniques may prove useful to assess the strength and pattern of adaptive evolution in a variety of evolving systems. They are especially powerful when assessing selection in fast-evolving populations, where temporal patterns become highly visible.http://deepblue.lib.umich.edu/bitstream/2027.42/112626/1/12862_2011_Article_1838.pd
Strength and tempo of selection revealed in viral gene genealogies
BACKGROUND: RNA viruses evolve extremely quickly, allowing them to rapidly adapt to new environmental conditions. Viral pathogens, such as influenza virus, exploit this capacity for evolutionary change to persist within the human population despite substantial immune pressure. Understanding the process of adaptation in these viral systems is essential to our efforts to combat infectious disease. RESULTS: Through analysis of simulated populations and sequence data from influenza A (H3N2) and measles virus, we show how phylogenetic and population genetic techniques can be used to assess the strength and temporal pattern of adaptive evolution. The action of natural selection affects the shape of the genealogical tree connecting members of an evolving population, causing deviations from the neutral expectation. The magnitude and distribution of these deviations lends insight into the historical pattern of evolution and adaptation in the viral population. We quantify the degree of ongoing adaptation in influenza and measles virus through comparison of census population size and effective population size inferred from genealogical patterns, finding a 60-fold greater deviation in influenza than in measles. We also examine the tempo of adaptation in influenza, finding evidence for both continuous and episodic change. CONCLUSIONS: Our results have important consequences for understanding the epidemiological and evolutionary dynamics of the influenza virus. Additionally, these general techniques may prove useful to assess the strength and pattern of adaptive evolution in a variety of evolving systems. They are especially powerful when assessing selection in fast-evolving populations, where temporal patterns become highly visible
Ecological and Evolutionary Dynamics of Influenza Viruses.
Host-pathogen interactions, especially those involving RNA viruses and bacteria, are often characterized by a convergence of ecological and evolutionary time scales. This work explores how such convergence affects the diversity of a fast-evolving RNA virus, influenza, in different host populations. The first study evaluates molecular evidence for a theory of H3N2 dynamics in humans. There is support for episodically strong, continuous positive selection on the hemagglutinin protein, and previously described punctuated changes in antigenicity are not driven by the addition of glycosylation sites. The neuraminidase, nucleoprotein, and matrix 2 proteins also show evidence of positive selection. The second study analyzes time series of serologically confirmed cases of H3N2, H1N1, and influenza B in patients in present-day St. Petersburg, Russia, from 1969 to 1991 to determine whether there is cross-immunity between heterologous strains. Results suggest a role for cross-immunity, but further investigation is necessary. Differences in intrinsic growth rates and rates of antigenic evolution might explain age-related patterns in incidence by virus type and subtype. The third study investigates the effects of heterogeneity in hosts’ immune responses on the outcome of strain competition. When immunodominance is skewed toward a single epitope, coexistence inevitably results. When multiple epitopes can be immunodominant, coexistence, limit cycling, chaotic dynamics, and competitive exclusion can occur. Increasing the diversity and breadth of host responses increases the range of cyclic, chaotic, and exclusive dynamics. The last study considers how host ecology affects the long term evolution of influenza’s host range, assuming a tradeoff in the virus’s preference for certain forms of host sialic acid receptor. A common outcome is the coexistence of specialists, and this outcome is more sensitive to interspecific transmission rates and host population densities than the strength of the tradeoff. Finally, I map three areas of future inquiry: the ability of spatial dynamics and constant antigenic evolution alone to restrict influenza virus diversity, implications of antibody affinity versus neutralization ability for vaccine development, and long-term strategies to manage influenza virus evolution. These studies show that a phylodynamic perspective will be invaluable in developing better predictive models of influenza.Ph.D.Ecology and Evolutionary BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/64670/1/cobey_1.pd
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Improving influenza vaccine virus selectionReport of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14–16 June 2010
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90035/1/j.1750-2659.2011.00277.x.pd
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