A Few Genetic Tweaks To Chinese Bird Flu Virus Could Fuel A Human Pandemic

A study published Thursday shows how a bird flu virus that's sickening and killing people in China could mutate to potentially become more contagious.

Just three changes could be enough to do the trick, scientists report in the journal PLOS Pathogens.

And the news comes just as federal officials are getting ready to lift a moratorium on controversial lab experiments that would deliberately create flu viruses with mutations like these.

Public health officials have been worried about this bird flu virus, called H7N9, because it's known to have infected more than 1,500 people — and killed 40 percent of them. So far, unlike other strains that more commonly infect humans, this deadly virus does not spread easily between people.

The fear is that if it mutates in a way that lets it spread more easily, the virus will sweep around the globe and take a heavy toll, because people's immune systems haven't ever been exposed to this type of flu before. Past pandemics caused by novel flu viruses jumping from animals or birds into people have killed millions.

"As scientists we're interested in how the virus works," says Jim Paulson, a biologist at The Scripps Research Institute. "We're trying to just understand the virus so that we can be prepared."

That's why he and his colleagues recently tinkered with a piece of the H7N9 flu — a protein that lets the virus latch onto cells. It's thought to be important for determining which species the virus can infect.

"So it's not the whole virus," says Paulson. "It's just a piece — just a fragment — that we can then study for its properties."

What they studied is how different changes affected the virus' ability to bind to receptors found on the surface of human cells.

It turns out that three small mutations made the fragment bind far more strongly to receptors found on human cells than to receptors from bird cells. Scientists know, from studying strains that led to past pandemics, that this kind of switch appears to be involved in enabling a bird flu virus to become transmissible between people.

"All we've done is to look at one of the properties that we're pretty certain is important," says Paulson, who cautions that additional genetic mutations might be necessary for this virus to become more contagious in humans. "So, just because we've changed the one property doesn't mean that that property alone is sufficient to let the virus transmit."

One way of finding out would be to test the effect of these mutations in the actual H7N9 virus. And he and a colleague did put in a proposal to the National Institutes of Health to modify the virus to explore what changes could make it transmissible among lab animals.

"And then the moratorium came out and so it wasn't reviewed," says Paulson.

That unusual moratorium, announced by the White House in 2014, halted federally funded research that might make flu viruses more dangerous.

It came after more than two years of debate among scientists about whether these experiments are too risky. Critics argue that the information gained isn't worth the possibility that a lab-created mutant flu might escape the lab, either by accident or because someone intentionally used it as a bioweapon. They argue that scientists shouldn't be in the business of taking deadly viruses and making them even worse.

"These are all legitimate concerns, in my view," says Paulson. Because of those concerns, he now wants to test these genetic changes — not in the H7N9 virus itself, but rather in a weakened strain of flu that can move from ferret to ferret, the lab stand-in for people in flu studies.

And it probably won't be long before he can propose such an experiment to the NIH, because the Department of Health and Human Services is almost finished with drafting a new policy that spells out how officials will review this type of flu experiment in the future.

"As soon as that policy is finalized, the moratorium will be lifted and NIH will move forward in concordance with that new policy. Our expectation is it will be very soon," says Carrie Wolinetz, acting chief of staff and associate director for science policy at the NIH. "We want to make sure that there is an appropriate level of review to seriously consider the balance of that benefit/risk equation in a way that allows us move forward responsibly."

One scientist who's been critical of deliberately creating potential pandemic pathogens is David Relman, a biologist at Stanford. If a scientist wanted to test the effect of these recently-identified mutations in a weakened lab strain of flu, he says, "I would be much more accepting of that kind of experiment."

But if researchers wanted to make these genetic changes in the actual H7N9 virus, he says, "I would be very hesitant, were they to want to do that. In fact, I would be reluctant to have them do that."

Relman notes that a policy guidance released in the last days of the Obama administration says work that could create a highly virulent, highly transmissible virus requires special scrutiny. "Now, the part I don't agree with," he says, "is they don't come right out and say, 'Let's not do that."

Other researchers, like Ron Fouchier of Erasmus Medical Center in the Netherlands, who receives NIH funding, have publicly argued for the need to modify H7N9 in the lab to see exactly what this virus might be capable of. They believe such research is essential to truly understand the threat.

"The rest of the world is moving forward with this type of experiment already," says Fouchier, whose genetic experiments with a different bird flu virus sparked a public outcry in 2011.

"And so the U. S. can either join or not join. It's up to them, but the work will continue," he says.

"I'm pretty sure that the U. S. government will start funding this research again," Fouchier says, "because this is clearly important work. In the flu field, this is one of the most important questions to be addressed: How do we identify, among thousands of viruses that cause outbreaks, those viruses that are going to cause the next pandemic?"

He's hoping to learn more about how officials will handle all this when a network of federally funded flu researchers meets next month in Atlanta.

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