How Zika Became So Dangerous For Babies

Sep 28, 2017
Originally published on September 28, 2017 6:56 pm

Scientists have started to unravel a key mystery about the Zika virus. And the findings are almost unbelievable.

"When I first started reading the study, I said, 'Oh, my gosh, that's amazing,' says molecular biologist Alysson Muotri, at the University of California, San Diego, who wasn't involved in the study.

The study — published Thursday in the journal Science — demonstrates how an obscure virus may have transformed into a global threat almost overnight.

For decades, Zika had been a relatively innocuous disease. Since its discovery in 1947, the mosquito-borne virus had been circulating around Africa and Asia, almost undetected. It caused only a mild illness — a fever, a rash and joint pain. About 80 percent of people had no symptoms at all. And outbreaks tended to be small.

Then, in 2015, all that changed. The virus caused a massive outbreak in Brazil. Women there started giving birth to babies with severe brain damage and abnormally small heads — a birth defect called microcephaly.

Scientists quickly linked the defect to an infection with Zika in utero. To date, about 3,000 babies in Brazil have microcephaly because of Zika, the Pan American Health Organization reports. Suddenly this obscure virus had turned into a global threat.

Then the big question became: Why? Why did the virus's behavior change so suddenly? Two main hypotheses emerged:

1. Perhaps Zika had always been raising the risk of microcephaly for babies, but the extra cases went undetected in many places because outbreaks were small. And the risk was low.

2. Or maybe the virus had evolved. Maybe in the past couple of years, it had mutated in a way that made the virus more toxic to fetal brains.

Now researchers in Beijing have evidence that the latter is true. A single mutation — just one change in the virus's genes — dramatically increases Zika's ability to damage fetal neurons and leads to more severe cases of microcephaly in mice, the team reports.

"In my naive perception, I thought the virus would have needed a combination of different mutations to start causing this severe form of microcephaly," Muotri says. "Finding a single mutation is sufficient is unexpected — and a bit scary."

The study estimates that Zika picked up this mutation sometime around 2012 and 2013, right before the first cases of microcephaly appeared in the Pacific Islands and before the outbreak began in Brazil.

"That timing is striking," says Hongjun Song, a neuroscientist at the University of Pennsylvania, who wasn't involved with the study.

"It adds more support to the possibility that this mutation is the causal factor," he adds. "But there's really no way to know for sure because we can't do the same experiments in humans."

In the new study, Cheng-Feng Qin and his colleagues at the Beijing Institute of Microbiology and Epidemiology analyzed different versions of Zika: three modern strains isolated from people in 2015 and 2016 and one older strain isolated in 2010.

When they injected the Zika strains into the brains of developing mice, the three modern versions caused 100 percent mortality. By comparison, the older strain killed fewer than 20 percent of the animals. The modern strain also caused more severe microcephaly than the old strain.

To figure out what makes the modern strains so deadly, the researchers sequenced the viruses' genomes and identified a handful of mutations that have cropped up in the virus over the past few years.

They then added these mutations — one by one — to the older strain to see if the mutations alter the virus's toxicity. One mutation stood out from the rest. The mutation boosted the older strain's ability to kill fetal neurons and cause microcephaly. The inverse was also true: Removing the mutation from the modern strain reduced its toxicity.

"This one mutation was required and sufficient for causing severe microcephaly in the mice," says Guo-li Ming, who is also a neuroscientist at the University of Pennsylvania and Song's collaborator.

Although this mutation is likely a huge piece of the Zika puzzle, it's not the complete picture, she says. Other mutations in the modern strain also boost the virus's ability to cause microcephaly.

"If you really look into the data," Ming says, "you see that the one key mutation doesn't completely convert the older strain into the modern strain, in terms of toxicity."

And the study also doesn't rule out the possibility that an environmental factor made the virus even more toxic to fetal brains in Brazil, Song says.

"It's not that the initial strain from Africa is completely innocuous for fetal brains or that the American strain causes microcephaly every time a pregnant woman is infected," Song says. "The two strains lie on a spectrum. And mutations have likely pushed the American strain toward the more toxic end of the spectrum."

Nevertheless, the study demonstrates how quickly viruses can evolve, Song says.

"It is a really a good example of what nature can do," he says. "And it's scary. One unlucky change — which happens all the time — can cause a big unlucky event down the road."

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Scientists say they have solved a mystery about the Zika virus. They think they've figured out why the virus became a global threat all of a sudden and started causing severe birth defects. As NPR's Michaeleen Doucleff reports, the study shows how quickly viruses can become extremely dangerous.

MICHAELEEN DOUCLEFF, BYLINE: When I received the study, I sent it to a biologist at UC San Diego who's at the forefront of Zika research. His name is Alysson Muotri, and he almost couldn't believe his eyes.

ALYSSON MUOTRI: When you sent it to me, I started reading. I said, oh, my gosh, that's amazing.

DOUCLEFF: Amazing because the study suggests something unexpected. One small change in Zika's genes made it a big threat for pregnant women. For decades, Zika had been a relatively harmless virus that causes only mild symptoms. But then in 2015, it began causing a severe type of birth defect called microcephaly in which babies are born with very small heads. Now researchers at the Chinese Academy of Sciences in Beijing say they know why. Zika mutated. The virus picked up one mutation that dramatically increased its ability to infect fetal brains.

MUOTRI: That single mutation can actually lead to more severe cases of microcephaly, more severe damage in the fetal brain.

DOUCLEFF: This almost sounds like the nightmare scenario, the virus mutating and becoming this very scary thing. Is this common?

MUOTRI: It is common. It happens all the time. Actually, there are several human disorders that's caused by a single mutation. So this happens all the time.

DOUCLEFF: But there are caveats to this study. Hongjun Song is a neuroscientist at the University of Pennsylvania. He says the big caveat is the experiments were performed in mice.

HONGJUN SONG: Mouse is the one model we have now to test the toxicity of the virus in animals, which is the best you can do because we can't really do that in humans.

DOUCLEFF: And the study, which appears in the journal Science, doesn't rule out the possibility that other factors - other mutations or something in the environment - made the virus even worse in South America. Nevertheless, Song says the findings are a bit foreboding.

SONG: I think it's just a little bit scary, right? So basically one unlucky change which happens all the time can cause very big, unlucky events down the road. So I think the lesson, I feel, is we all need to be prepared.

DOUCLEFF: Because the next big outbreak is likely just around the corner. Michaeleen Doucleff, NPR News.

(SOUNDBITE OF EMUNE AND MUJO'S "DETROIT STREETS") Transcript provided by NPR, Copyright NPR.