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: 10.35). 11/2010; 28(6):1755-67. DOI: 10.1093/molbev/msq317
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza A is a highly contagious respiratory virus in constant evolution and represents a threat to both veterinary and human public health. IA viruses (IAVs) originate in avian reservoirs but may adapt to humans, either directly or through the spillover to another mammalian species, to the point of becoming pandemic. IAVs must successfully be able to (i) transmit from animal to human, (ii) interact with host cells, and (iii) transmit from human to human. The mechanisms by which viruses evolve, cause zoonotic infections, and adapt to a new host species are indeed complex and appear to be a heterogeneous collection of viral evolutionary events rather than a single phenomenon. Progress has been made in identifying some of the genetic markers mainly associated with virulence and transmission; this achievement has improved our knowledge of how to manage a pandemic event and of how to identify IAVs with pandemic potential. Early evidence of emerging viruses and surveillance of animal IAVs is made possible only by strengthening the collaboration between the public and veterinary health sectors.
    Influenza and Other Respiratory Viruses 09/2013; 7(s2). · 1.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The sociological and biological factors which gave rise to the three pandemic waves of Spanish influenza in England during 1918-19 are still poorly understood. Symptom reporting data available for a limited set of locations in England indicates that reinfection in multiple waves occurred, suggesting a role for loss of infection-acquired immunity. Here we explore the role that changes in host immunity, driven by a combination of within-host factors and viral evolution, may play in explaining weekly mortality data and wave-by-wave symptomatic attack-rates available for a subset of English cities. Our results indicate that changes in the phenotype of the pandemic virus are likely required to explain the closely spaced waves of infection, but distinguishing between the detailed contributions of viral evolution and changing adaptive immune responses to transmission rates is difficult given the dearth of sero-epidemiological and virological data available even for more contemporary pandemics. We find that a dynamical model in which pre-pandemic protection in older "influenza-experienced" cohorts is lost rapidly prior to the second wave provides the best fit to the mortality and symptom reporting data. Best fitting parameter estimates for such a model indicate that post-infection protection lasted of order months, while other statistical analyses indicate that population-age was inversely correlated with overall mortality during the herald wave. Our results suggest that severe secondary waves of pandemic influenza may be triggered by viral escape from pre-pandemic immunity, and thus that understanding the role of heterosubtypic or cross-protective immune responses to pandemic influenza may be key to controlling the severity of future influenza pandemics.
    Epidemics 09/2014; 8C:18-27. · 2.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Please see later in the article for the Editors' Summary.
    PLoS Medicine 05/2014; 11(5):e1001646. · 15.25 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014