Health A Scarier Zika
A single mutation may make the virus more devastating to newborns
seen among children infected with the Zika virus have haunted many of the people who live in regions where mosquitoes carry the pathogen, including the U.S., South America, Africa and Southeast Asia. It turns out that a single genetic change in the virus may be responsible.
The defect, known as microcephaly, wreaks all kinds of physical and developmental havoc. Children with microcephaly may have seizures, hearing loss, difficulty seeing or moving, and may not learn to sit, stand or walk at the same rate as other children. They may also have intellectual disabilities. At least 3,000 children around the world have been born with microcephaly or another Zika-related brain birth defect.
not always a common birth defect in children affected by Zika, and the problem may have gone unnoticed during earlier outbreaks because fewer infected women were pregnant. But as the epidemic changed—expanding in Brazil, most notably—the problem became more noticeable, says Dr. Michael Diamond, an infectious diseases specialist at the Washington University School of Medicine in St. Louis.
“[Zika] will come back at some point,” says Diamond. “I can’t tell you when, but it will come back at some point. And if it comes back, are we going to be in the same place that we were last time—with nothing—or are we going to continue to study it, understanding it might come back worse than it is now?”
A group of Chinese researchers led by Cheng-feng Qin, a virologist at the Beijing Institute of Microbiology and Epidemiology, wondered if the virus had mutated, becoming more virulent and damaging to the developing human brain. To test this theory, he separated newborn mice into four groups and injected one of four different strains of the virus into their brains. One strain was associated with a 2010 outbreak; three strains were isolated during the outbreak from 2015 to 2016. He also tested the virus on human brain stem cells.
Mice infected with one particular strain, called VEN/2016, developed brains that were far smaller than those of mice infected with other strains. Their brains were also
“[Zika] will come back at some point. I can’t tell you when, but it will come back.”
smaller after being infected with a virus created to carry just one of the newer mutations found in VEN/2016. That mutation changed one component of a protein called prm.
The single genetic abnormality alters the course of the disease. “This specific mutation can indeed make the virus more aggressive,” says Alysson Muotri, who researches the Zika virus at the University of California, San Diego, but was not involved in the new paper.
The breakthrough, published last month in Science, could be crucial for the treatment of future outbreaks. Although concerns over Zika have diminished since last year, the problem has not disappeared. With so many areas in North America now covered in stagnant floodwaters, questions linger about what impact recent storms could have on the transmission of the virus. The new finding is a first step toward knowing how and why the Zika virus causes birth defects—and which forms of the virus might be particularly dangerous.
Although the results of Qin’s research were strong, the methodology left many researchers with questions. Injecting the virus straight into a mouse’s brain is not the usual path the virus takes to a developing fetus. In most cases, a mosquito bites a pregnant woman, then the virus spreads through her body and crosses the placenta to reach the womb. “[Injecting it] inside the brain, it works. The question is, Does it work outside the brain?” says Jean Pierre Schatzmann Peron, an
immunologist at the University of São Paulo in Brazil.
The answer may be no. The mutated protein identified in Qin’s study is found on the surface of the virus. That might make it more “visible” to the mother’s immune system, enabling the body to attack the invader before it reaches the fetus.
Exactly why this mutation makes the virus work differently is unclear, says Schatzmann Peron, and it may not be the sole perpetrator. The more aggressive Zika virus could be exacerbated by other issues that make an infant even more susceptible to microcephaly.
“This [mutation] can change the biology of the virus, but it doesn’t fully explain what’s going on,” says Muotri. Environmental factors, the person’s genetic background and previous exposure to other viruses or vaccines could all be involved. “It’s not only about the viral genetics,” says Muotri. “There are probably other factors that play a role.”
Qin and his team are now searching for those factors, but Diamond says other approaches are also needed. Ideally, he says, scientists would use similar experiments with monkeys or chimpanzees, allowing the virus with this mutation to infect the animals from mosquitos and then watching how it affects fetal development.
Though the mosquito that spreads Zika can be found in several European countries, according to the World Health Organization, the risk for people who don’t travel outside of Europe has stayed relatively low. Just over 2,000 cases of Zika were reported across Europe in 2016, nearly all of which were associated with recent travel.
But as Diamond points out, the virus could re-emerge anytime, and we need to be prepared.
BABY STEPS Cheng-feng Qin, right, led, a group of Chinese researchers who found evidence that, at one point, the Zika virus became more aggressive.
OUTBREAK With so many areas in North America now covered in stagnant floodwaters, questions linger about what impact recent storms could have on the mosquito-borne virus.