MRC National Institute for Medical Research, London
Science for Health
Host shifts in influenza
17 November 2009
Influenza A is unusual in being an old disease, a recurring disease, and an ‘emerging’ disease. Influenza A viruses are found in humans as well as in other animals including swine, horses, sea mammals, and birds. Waterfowl are considered the natural reservoir of Influenza A. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, waterfowl virus genomic segments are able to shift to a human host, either in toto or by combining with material that underwent a previous host shift event. Thus genetic material from waterfowl viruses can be introduced into viruses affecting the human population, causing a host shift and resulting in worldwide influenza pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Unfortunately, it is difficult to determine whether a mutation is due to adaptation to the new host, or it has occurred through random drift. Comparisons of amino acid frequencies in viruses from the two hosts cannot easily distinguish between those that accidentally accompanied the host shift event and those that were actually associated with different selective constraints acting on the viruses in the two hosts.
Richard Goldstein (pictured) and his group in NIMR's Division of Mathematical Biology, working with Alan Hay in the Division of Virology, have described a novel phylogenetic approach to identifying locations where the nature of the selective pressure exerted on the location has changed corresponding to the host shift event. Their approach considers not only changes in the magnitude of selection constraints, but also changes in its nature, represented as the relative propensity for the different amino acids. They did this by considering two different models for each site, a homogeneous model where the selective constraints are independent of host, the other a non-homogeneous model where the selective constraints depend upon the host. The likelihood ratio test can then determine the level of statistical support for rejecting the null hypothesis of no such dependence.
Selective constraint strengths for viral sites in Avian and Human influenza
Strength of selective constraints for viral sites identified (FDR < 0.05) as under different selective constraints in avian and human hosts. Colour coding refers to specific gene: HA (red), NA (blue), M1 (black), M2 (brown), NP (green), NS1 (orange), PA (cyan), PB1 (purple), PB2 (magenta). Selective sites are labelled..
Identifying the changes that have occurred in the past can provide important clues about how viruses shift hosts, and how surveillance for new influenza threats should be targeted. The approach we describe is of wide applicability when the timing of the change of selective constraints is known in advance.
Richard Goldstein
Original article
The research findings are published in full in:
Asif U. Tamuri, Mario dos Reis, Alan J. Hay, Richard A. Goldstein (2009)
Identifying changes in selective constraints: Host shifts in influenza
PLoS Computational Biology, 5(11): e1000564. Article full text
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