Charting the Host Adaptation of Influenza Viruses

Division of Mathematical Biology, National Institute for Medical Research, London, United Kingdom.
Molecular Biology and Evolution (Impact Factor: 9.11). 11/2010; 28(6):1755-67. DOI: 10.1093/molbev/msq317
Source: PubMed


Four influenza pandemics have struck the human population during the last 100 years causing substantial morbidity and mortality. The pandemics were caused by the introduction of a new virus into the human population from an avian or swine host or through the mixing of virus segments from an animal host with a human virus to create a new reassortant subtype virus. Understanding which changes have contributed to the adaptation of the virus to the human host is essential in assessing the pandemic potential of current and future animal viruses. Here, we develop a measure of the level of adaptation of a given virus strain to a particular host. We show that adaptation to the human host has been gradual with a timescale of decades and that none of the virus proteins have yet achieved full adaptation to the selective constraints. When the measure is applied to historical data, our results indicate that the 1918 influenza virus had undergone a period of preadaptation prior to the 1918 pandemic. Yet, ancestral reconstruction of the avian virus that founded the classical swine and 1918 human influenza lineages shows no evidence that this virus was exceptionally preadapted to humans. These results indicate that adaptation to humans occurred following the initial host shift from birds to mammals, including a significant amount prior to 1918. The 2009 pandemic virus seems to have undergone preadaptation to human-like selective constraints during its period of circulation in swine. Ancestral reconstruction along the human virus tree indicates that mutations that have increased the adaptation of the virus have occurred preferentially along the trunk of the tree. The method should be helpful in assessing the potential of current viruses to found future epidemics or pandemics.

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Available from: Mario dos Reis, Mar 29, 2014
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    • "Virological and genealogical studies of the 1918 pandemic virus, whilst based on limited genetic samples, imply that pH1N11918 had been circulating in mammals for several years prior to the pandemic, and likely co-circulated with seasonal and swine lineages of H1N1 (Smith et al., 2009; dos Reis et al., 2011). In more contemporary pandemics severe second waves of pandemic transmission may have been triggered by changes in the circulating virus (Viboud et al., 2005). "
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    Epidemics 09/2014; 8C:18-27. DOI:10.1016/j.epidem.2014.07.004 · 1.87 Impact Factor
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    • "Certain pathogens can shift from one host to the next via ecological fitting, using traits already present,31 or by pre-adaption in the reservoir host.34 One example is the 2009 pandemic H1N1 influenza A virus that showed evidence of pre-adaption to humans during its circulation in swine.35 However, adaptation in the novel host is often required for successful infection and subsequent sustained transmission between new hosts. "
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    ABSTRACT: Gaining insight in likely disease emergence scenarios is critical to preventing such events from happening. Recent focus has been on emerging zoonoses and on identifying common patterns and drivers of emerging diseases. However, no overarching framework exists to integrate knowledge on all emerging infectious disease events. Here, we propose such a conceptual framework based on changes in the interplay of pathogens, hosts and environment that lead to the formation of novel disease patterns and pathogen genetic adjustment. We categorize infectious disease emergence events into three groups: (i) pathogens showing up in a novel host, ranging from spill-over, including zoonoses, to complete species jumps; (ii) mutant pathogens displaying novel traits in the same host, including an increase in virulence, antimicrobial resistance and host immune escape; and (iii) disease complexes emerging in a new geographic area, either through range expansion or through long distance jumps. Each of these categories is characterized by a typical set of drivers of emergence, matching pathogen trait profiles, disease ecology and transmission dynamics. Our framework may assist in disentangling and structuring the rapidly growing amount of available information on infectious diseases. Moreover, it may contribute to a better understanding of how human action changes disease landscapes globally.
    Emerging Microbes and Infections 02/2013; 2(e5). DOI:10.1038/emi.2013.5 · 2.26 Impact Factor
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    • "The polymerase genes seem to be involved in host adaptation , and there is evidence of several amino acid substitutions after the host shift (Taubenberger et al. 2005; dos Reis et al. 2011). Tamuri et al. (2009) "
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    ABSTRACT: Estimation of the distribution of selection coefficients of mutations is a long-standing issue in molecular evolution. In addition to population-based methods, the distribution can be estimated from DNA sequence data by phylogenetic-based models. Previous models have generally found unimodal distributions where the probability mass is concentrated between mildly deleterious and nearly neutral mutations. Here we use a sitewise mutation-selection phylogenetic model to estimate the distribution of selection coefficients among novel and fixed mutations (substitutions) in a data set of 244 mammalian mitochondrial genomes and a set of 401 PB2 proteins from influenza. We find a bimodal distribution of selection coefficients for novel mutations in both the mitochondrial data set and for the influenza protein evolving in its natural reservoir, birds. Most of the mutations are strongly deleterious with the rest of the probability mass concentrated around mildly deleterious to neutral mutations. The distribution of the coefficients among substitutions is unimodal and symmetrical around nearly neutral substitutions for both data sets at adaptive equilibrium. About 0.5% of the nonsynonymous mutations and 14% of the nonsynonymous substitutions in the mitochondrial proteins are advantageous, with 0.5% and 24% observed for the influenza protein. Following a host shift of influenza from birds to humans, however, we find among novel mutations in PB2 a trimodal distribution with a small mode of advantageous mutations.
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