In a study designed to simulate how the pandemic 2009 influenza (pH1N1) virus might have evolved, researchers say it took only nine passages in pigs for a virus to gain "greatly enhanced virulence and transmissibility" in pigs, guinea pigs, and ferrets.
Writing in the Journal of Virology, the team of Chinese, American, and British researchers says there is no clear evidence that the pH1N1 virus stemmed from a direct precursor in pigs. They started with a reassortant H1N1 virus that was phylogenetically similar to pH1N1 in that it had two gene segments from a Eurasian avian-like H1N1 swine flu virus and six segments from a triple-reassortant H3N2 virus, but it had limited virulence and transmissibility in animal models.
The authors infected a pig with this virus, collected samples from the animal 4 days later, and used them to infect another pig, repeating the process until nine pigs had been infected. They found that the severity of infection increased with each pig in the series.
When the researchers analyzed viruses collected from the last pig in the series, they found that they shared five amino acid mutations and that mutations in the hemagglutinin (HA) protein differed greatly between the upper and lower respiratory tracts. Three representative viral clones were found to have enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets, compared with the parent virus.