NATURE 

Mutant-flu paper published

Controversial study shows how dangerous forms of avian influenza could evolve in the wild.

An engineered influenza virus based on a haemagglutinin protein from H5N1 avian influenza, with just four mutations, can be transmitted between ferrets, emphasizing the potential for a human pandemic to emerge from birds.

H5N1, commonly known as bird flu, is highly pathogenic and often lethal in humans, but it cannot spread efficiently between people and cases seem to be rare. To find out if H5N1 could evolve easy transmissibility between humans, Kawaoka and his team mutated its haemagglutinin (HA) gene, which produces the protein that the virus uses to stick itself to host cells. Because flu viruses in the wild can also gain new properties by swapping genes, the researchers combined this gene with seven others from a highly transmissible flu virus, the H1N1 strain that caused a pandemic in 2009.

Kawaoka found that the hybrid virus could spread between ferrets in separate cages after acquiring just four mutations. Three of these allow the HA protein to stick to receptor molecules on mammalian cells, and the fourth stabilizes the protein. “Before we initiated this experiment, we knew that receptor specificity is important,” says Kawaoka. “We didn’t know what else was needed.”

Worryingly, some Middle Eastern H5N1 strains can already recognize human receptors². Kawaoka’s work suggests that they could be just one stabilizing mutation away from being able to spread between humans. Discovering “that HA needs to be stable to be transmissible through the air between mammals” is a key finding, says influenza virologist Wendy Barclay at Imperial College London.