Did Zika’s recent mutations let it explode as a global threat?

Don’t get pregnant, at least for now. That is the chilling warning from governments battling the Zika pandemic, as evidence mounts that the mosquito-borne virus can cause severe birth defects.

As the scale of the impact starts to emerge, scientists are scrambling to learn more about the little-known virus. Is it evolving to be more severe and contagious in humans? Or has it taken off so aggressively simply because someone carried it to a new place with the right mosquitoes?

Zika virus got a foothold in the Americas, via Brazil, early last year. Since then it is estimated to have infected up to 1.3 million people there, and to have broken out in 25 countries where it was previously unknown, across Asia, Africa and the Pacific. This includes 12 countries in the Americas that have been infected since mid-December.

Travellers with Zika are turning up as far afield as New York and the UK. In places where the Aedes mosquitoes that carry the virus live, such infected people could spread it further.

Aedes mosquitoes occur throughout the tropics and into the temperate zone, including southern Europe and as far north in the US as Long Island. The World Health Organization announced today that in the Americas only Canada and continental Chile are free of Aedes – hence the virus could spread everywhere else.

More efficient virus?

What is worrying virologists, says Paolo Zanotto of the University of Sao Paulo in Brazil, is that before 2000, Zika wasn’t known to spread widely among humans or cause the kind of complications we are seeing today, such as stunted brain development in fetuses and the potentially fatal neural disorder Guillain-Barré syndrome (see “Zika: symptoms and complications”, below).

It evolved in Africa as an infection of forest animals – possibly primates – that occasionally infected people, but never spread. Decades ago it invaded some parts of South-East Asia, abandoning animals and spreading solely among humans, but went no further.

Now that Asian strain is exploding. It infected 75 per cent of Yap islanders in Polynesia in 2007 and caused a massive outbreak in French Polynesia in 2013. That outbreak was followed by a rise in Guillain-Barré syndrome and brain damage in newborns.

“I suspect the virus may have changed,” says Scott Weaver of the University of Texas in Galveston. It may be able to infect mosquitoes more easily, or multiply to higher levels in humans, so a mosquito is more likely to ingest some and infect her next victim.

In work awaiting peer review, Zanotto reports that Zika has recently acquired subtle changes to its genome, which may allow it to hijack human cells more efficiently.

Crowded cities

But both Zanotto and Weaver stress that the virus’s apparent leap in virulence and transmission might just be down to it invading virgin territory, where people have no previous exposure and therefore no immunity.

Other factors might have pushed it beyond its South-East Asian stronghold. Increasingly dense urban populations where humans and mosquitoes are crowded together will have led to more infections, making it more likely that someone with high levels of virus in their blood would carry Zika somewhere else with Aedes mosquitoes.

Several labs are gearing up to see if recent strains are better at infecting Aedes – and have the mutations to match. After discovering molecules on Zika that resemble some on dengue virus, Zanotto is starting a trial to see if exposure to one causes damaging immune reactions to the other. He is worried that getting Zika might leave people vulnerable to a more serious form of dengue, and vice versa.

“There are a lot of studies going on in Brazil,” says Maurício Nogueira of the Medical Faculty of São José in Rio Preto, Brazil, but results will take time, and the epidemic is growing. “We are trying to change the tyres with the car running.”

Meanwhile, virologists worry about which virus will next leap from obscurity. “This will not stop with Zika,” warns Ab Osterhaus of the University of Rotterdam in the Netherlands, who is looking at recent mutations in the virus. “We must get better at picking up these things earlier, and intervening.”