Much discussion (including in this blog) has surrounded the question of the origin of the H1N1 influenza A variant(s) (‘swine origin influenza virus’ or S-OIV) involved in the recent outbreak, initially in Mexico, of swine flu. Is it ‘really’ swine flu or is it ‘really’ a form of bird flu that transmitted to swine, or what? A recent online publication by Smith et al., with the same title as that in the apodosis of this blog (apologies to George Gershwin for the protasis), describes work partly funded by BBSRC that sheds considerable light on the answers. This is especially timely given the raising by the WHO of the present outbreak to ‘level 6’ pandemic status.
Smith and colleagues used phylogenetic methods based on Bayesian software designed for this purpose to analyse the sequences of 796 published influenza genome sequences from avian, pig and human isolates, plus 15 new swine flu sequences, and to estimate when the sequences of the individual portions of the genome encoding proteins most credibly entered the reassorted S-OIV strain.
The S-OIV virus turns out to have been derived from several viruses circulating in American and Eurasian swine, and the phylogenetic methods light up a number of very interesting features. The first is that the initial transmission to humans occurred several months before recognition of the outbreak. The rate of evolutionary change was not atypical, and phylogenetic estimates of the gaps in genetic surveillance indicate a long period of unsampled ancestry before the S-OIV outbreak. Thus, the reassortment of swine lineages may have occurred years before human emergence. This ‘unsampled history’ of the epidemic means that the nature and location of the genetically closest swine viruses reveal rather little about the immediate origin of the epidemic, save that the effective origin does indeed seem to have been in swine. This is consistent with the widely held view that while most pigs are thought to be moderately tolerant of most human strains of influenza A, pigs could serve as an important reservoir for the production and selection of mutant virions with the potential to infect humans. It remains unknown as to whether strains that are virulent in pigs might also be virulent in humans, but these findings certainly raise the possibility that mixing and persistence of new genetic elements in swine can result in the emergence of viruses with pandemic potential in humans, just as happened in the case of the avian influenza strains that had become ‘Hong Kong’ flu.
As I commented in our press release on this (the story has already been picked up by Science-so what? and other outlets), this work of Smith et al. is a particularly nice example of the use of modern genomics and bioinformatics methods for solving complex biological problems, and one that has immediate social benefits. The paper itself also includes some excellent methods of data visualisation. Next month we shall be launching our own Genome Analysis Centre, in which bioinformatics methods and software for the analysis of large-scale and complex genomic data will be to the fore. Meanwhile, we have just announced a consultation on the use of next-generation sequencing methods. The era of data-intensive science is beginning, and it is necessarily so.
- Bell, G., Hey, T. & Szalay, A. (2009). Beyond the data deluge. Science 323, 1297-8
- Drummond, A. J. & Rambaut, A. (2007). BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7, 214. Full paper (PDF)
- Shortridge, K. F., Webster, R. G., Butterfield, W. K. & Campbell, C. H. (1977). Persistence of Hong Kong influenza virus variants in pigs. Science 196, 1454-5
- Smith, G.J.D., Vijaykrishna, D., Bahl, J., Lycett, S.J., Worobey, M., Pybus, O.G., Ma,S.K., Cheung, C.L., Raghwani, J., Bhatt, S., Peiris, J.S.M., Guan, Y. & Rambaut, A. (2009) Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature online doi:10.1038/nature08182. Full text (PDF)
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