Swine flu is at the forefront of the news again, so it is timely that an analysis of the origins of the virus has now been published online in Nature. A team of researchers from the UK, Hong Kong and the US used evolutionary analysis to reconstruct how and when this strain of the virus (which is now referred to as swine-origin influenza-A (H1N1) virus, or S-OIV) developed. By comparing the genome sequences of the pandemic strain with 100s of other strains from pigs, birds and humans that represent the full spectrum of influenza A viruses, the team was able to build a family tree of S-OIV and date its emergence.
Their analysis shows that S-OIV is derived from several viruses already circulating in pigs, some of which were originally of avian or human origin. The initial transmission of S-OIV to humans occurred several months before the outbreak was recognised.
The origin of S-OIV is shown nicely in this figure from the paper (see here for a larger version)
The eight dots you can see on the far right of this diagram represent the 8 parts of the genome of S-OIV, and by tracing back the lines you can see their origin. H1N1 (classical swine) viruses have existed in pigs from North America and Eurasia for at least 80 years. The diagram shows that over the last 30 years H1N1 viruses from birds (green lines) and H3N2 viruses from humans (blue lines) have been mixing with the classical swine viruses (where the lines enter the pink part of the diagram) to create “triple-reassortant” viruses. Domestic pigs make excellent mixing vessels for viruses, and the movement of pigs between Eurasia and North America has aided and abetted these reassortment events. S-OIV shows striking similarities with some newly-sequenced swine flu strains from Hong Kong, which suggests that the predecessors of S-OIV were widely distributed around the globe.
By counting the number of changes between the sequence of S-OIV and its closest relatives, the timing of the reassortments that led to the pandemic strain were dated to between 9 and 17 years ago, depending on the genomic segment. So this means that the immediate ancestors of S-OIV have been present in pigs for about a decade, and have been circulating undetected during that time. The amount of sequence diversity within the pandemic strain in humans suggests that S-OIV made the leap to humans around January 2009 – a good 2 months before it was detected. However, the authors weren’t able to pinpoint the immediate origin of the pandemic strain, because a lack of sampling of swine flu viruses from around the world has produced some large gaps in the genetic records.
The researchers found no evidence of changes in the viral sequence that would suggest S-OIV has adapted to human hosts, or increased in virulence. This is consistent with the fact that the current outbreak is associated with relatively mild symptoms. However there were some signs that the molecular evolution of the virus may be speeding up. To work out how fast the viral genes are changing, the researchers measured the number of mutations in the viral gene sequences that produce changes in the protein sequence (non-synonymous changes). They found that the genes of S-OIV have a higher proportion of non-synonymous changes than the genes from other strains, which may indicate the virus is adapting to its new host. But don’t panic just yet – another, equally plausible explanation is that the increased survellience of the current strain means that mutations are more likely to be detected. Only time will tell which of the two explanations is correct.
The authors highlight the need for more systematic surveillance of influenza viruses in pigs from around the world. The lack of sampling meant that not only was this strain able to persist and evolve for many years without being detected, but it has made it difficult to determine the immediate origin of the current epidemic.
For more reading and reasoned discussion on swine flu, see Effect Measure.
Smith, G., Vijaykrishna, D., Bahl, J., Lycett, S., Worobey, M., Pybus, O., Ma, S., Cheung, C., Raghwani, J., Bhatt, S., Peiris, J., Guan, Y., & Rambaut, A. (2009). Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic Nature DOI: 10.1038/nature08182