Gene swapping makes H7N9 a moving target

New China bird flu a mix of 3 avian flu strains

LONDON, April 15, (RTRS): A new bird flu virus that has killed 13 people in China is still evolving, making it hard for scientists to predict how dangerous it might become.

Influenza experts say the H7N9 strain is probably still swapping genes with other strains, seeking to select ones that might make it fitter.

If it succeeds, the world could be facing the threat of a deadly flu pandemic. But it may also fail and just fizzle out.

The virus’ instability also raises questions about whether H7N9 might become resistant to antiviral drugs such as Roche’s antiviral drug Tamiflu, a possibility already suggested by analyses of genetic data available on the strain so far.

“Even with just the three (gene) sequences we have available, there’s some evidence that one doesn’t quite fit with the other two. So we might think this virus is still fishing around for a genetic constellation that its happy with,” said Wendy Barclay, a flu virologist at Imperial College London.

“Maybe there are other viruses out there that it is still exchanging genes with until it gets to a stable constellation.”

To be able to say with any confidence whether this new strain, which before March had never been seen in humans, could go on to cause a pandemic, scientists need to know a lot more.

So far, genetic sequence data from samples from three H7N9 victims and posted on the website of GISAID, the Global Initiative on Sharing All Influenza Data, show the strain is a so-called “triple reassortant” virus with a mixture of genes from three other flu strains found in birds in Asia.

Writing in the New England Journal of Medicine last week, researchers who conducted a detailed analysis of the strain’s origin said it seemed that so far the reassortment of genes to make H7N9 had taken place in birds rather than in humans or in any other mammal — a somewhat reassuring sign.

Barclay said this may continue, and could mean it is some time before the strain finds a form in which it can spread swiftly and efficiently in bird populations.

Yet genetic analyses also show the virus has already acquired some mutations that make it more likely be able to spread between mammals, and more able to spark a human pandemic.

A study in the online journal Eurosurveillance by leading flu experts Yoshihiro Kawaoka of the University of Wisconsin and Masato Tashiro at the National Institute of Infectious Diseases in Tokyo, said the H7N9 sequences “possess several characteristic features of mammalian influenza viruses, which are likely to contribute to their ability to infect humans”.

These features, the scientists wrote, “raise concerns regarding their pandemic potential”.

That sentiment was echoed on Saturday by the World Health Organization (WHO), which said “genetic changes seen among these H7N9 viruses suggesting adaptation to mammals are of concern” and warned: “Further adaptation may occur”.

While experts take some comfort in the lack of evidence so far that H7N9 is passing from person to person — a factor that would dramatically increase its pandemic potential — they are find little comfort in not yet knowing how the 60 or so people confirmed as having this flu strain became infected.

“We know H7 viruses can spill over into humans ... and for me the most important thing to find out now is from which species do we think this H7N9 is spilling over,” said An Osterhaus, head of viroscience of the Erasmus Medical Centre in the Netherlands.

“Is it one species? Are there different species? At this stage we are still lacking a lot of data.”

He said rigorous surveillance of wild birds, such as ducks and quail, and poultry such as chickens, as well as wellknown flu-carrying mammals such as pigs, should yield answers.

Recent pandemic viruses — including the H1N1 “swine flu” of 2009/2010 — have been mammal and bird flu mixtures. Experts say these hybrids are more likely to be milder, because mammalian flu tends to make humans less severely ill than bird flu.

Pure bird flu strains — like the new H7N9 strain and like the H5N1 strain that has killed around 371 of 622 the people it has infected since 2003 — are generally more deadly for people.

The world’s worst known pandemic, the “Spanish flu” of 1918 that killed more than 50 million people, was a bird flu that had picked up gene mutations that enabled it to spread efficiently in humans.

David Heymann, a flu expert and head of Britain’s Chatham House Centre on Global Health Security, said it is impor- tant to put the discovery of H7N9 in humans into the context of modern-day scientific capability.

He said that in the years since the outbreak of Severe Acute Respiratory Syndrome (SARS) in China in 2003, there has been a significantly increased focus on detecting and reporting flu-like respiratory infections in Asia and across the world.

The harder scientists look, he said, the more likely they are to find viruses that are potentially threatening but may equally be the sort of events that in the past might have flared up and petered out again under the flu surveillance radar.

That said, he stressed this is no time to relax.

“Influenza viruses are very unstable. And (any) mutation is a random event — so nobody can predict when it will happen,” he said. “You can’t take your eye off anything. You have to keep you eye on everything.”