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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    • "Three models concerning the evolutionary rates are implemented, as described by Yang and Rannala (2006) and Rannala and Yang (2007): The strict molecular clock, the independent-rates model and the correlatedrates model. The likelihood, f [D|z,x,r,] in Equation (1), is calculated using either Felsenstein (1981)'s pruning algorithm or the large-sample approximation based on the Taylor expansion of the log likelihood (Thorne et al. 1998; dos Reis and Yang 2011). Details of those parts of the Bayesian analysis have been described before and are not repeated here. "
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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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