A single genetic change — or mutation — made the Zika virus far more dangerous, a new study suggests. That change upped the ability of the virus to kill nerve cells in the brain of a developing baby.
The mutation changed just one amino acid in a protein that the gene instructs a cell to make. That altered protein helps the Zika virus kill brain cells more easily. It also may increase the risk of a birth defect called microcephaly (My-kroh-SEFF-uh-lee). Babies born with this condition have heads and brains that are abnormally small.
Researchers reported their new results September 28 in Science.
Those scientists calculated that the mutation arose around May 2013. This was shortly before a Zika outbreak in French Polynesia. That’s a nation of islands in the South Pacific.
Mosquitoes spread the virus, which was discovered decades ago. But Zika wasn’t linked to high rates of microcephaly until a Brazil outbreak in 2015 and 2016. That’s when high numbers of women infected with Zika started giving birth to babies with small heads.
Researchers weren’t sure why Zika suddenly seemed to cause this birth defect, says Pei-Yong Shi. He is a virologist at the University of Texas Medical Branch at Galveston. Researchers have considered several possibilities. Maybe the virus caused microcephaly before, but no one noticed. Perhaps the immune systems of people in South America just didn’t know how to fight it. Maybe they had a higher genetic risk. Or perhaps some earlier infection with a different virus somehow made Zika worse.
Shi and a team in China had a different idea. They thought a change in the virus itself might be responsible for the birth defect.
Strains are microbes that belong to the same species but differ slightly in their genes and behaviors. The researchers compared a strain of Zika that came from a patient in Cambodia in 2010 to three other strains. Those others came from patients in 2015 or 2016 who had become infected in South America (Venezuela), on a South Pacific island (Samoa) and on a Caribbean island (Martinique). The team found each of these three strains from the recent epidemic shared seven genetic differences from the Cambodian virus.
Researchers then made seven versions of the Cambodian virus. Each of these lab-made types contained one — and only one — of the different gene versions that had been seen in the epidemic strains. The team then infected the brains of fetal mice with these tweaked versions of the Cambodian strain.
A strain with one of the mutations seen in the epidemic version of the virus killed more brain cells in fetal mice than the earlier, Cambodian strain did. This mutant virus also attacked and killed human brain cells that were grown in lab dishes.
“That’s pretty convincing evidence that [that mutation] at least plays some role in what we’re seeing now,” says Anthony Fauci. He directs the National Institute of Allergy and Infectious Diseases. It’s part of the National Institutes of Health in Bethesda, Md.
The mutation changes an amino acid in a protein that Zika instructs cells to make. That protein is called prM. It helps the virus mature within infected cells. It also helps them get out of those cells to infect others. Shi and colleagues don’t yet know why this protein variant should help the virus kill brain cells, too.
The change in prM probably isn’t the whole reason Zika may cause smaller brains, Shi says. The Cambodian strain also led to the death of a few brain cells. But it may not kill enough to cause the birth defect. Shi and his colleagues believe other changes in the virus exaggerate its risks. In May, for instance, his team described another mutation seen in the epidemic strains. It makes Zika dangerous in a different way. It makes it easier for virus to infect mosquitoes.
Brain cells from different people vary in their susceptibility to Zika infections, says Scott Weaver. He’s an infectious-disease researcher. Although he also works at the University of Texas Medical Branch, he was not part of Shi’s team. Weaver says scientists need to do more work. They should study cells from more people to see how the different versions of virus affect them. The scientists also should probe Zika’s effects in nonhuman primates. If they respond similarly, that might confirm that this mutation is really behind microcephaly.
allergy The inappropriate reaction by the body’s immune system to a normally harmless substance. Untreated, a particularly severe reaction can lead to death.
behavior The way something, often a person or other organism, acts towards others, or conducts itself.
Caribbean The name of a sea that runs from the Atlantic Ocean in the East to Mexico and Central American nations in the West, and from the southern coasts of Cuba, the Dominican Republic and Puerto Rico down to the northern coasts of Venezuela and Brazil. The term is also used to refer to the culture of nations that border on or are islands in the sea.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
colleague Someone who works with another; a co-worker or team member.
epidemic A widespread outbreak of an infectious disease that sickens many people (or other organisms) in a community at the same time. The term also may be applied to non-infectious diseases or conditions that have spread in a similar way.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
genetic Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.
immune (adj.) Having to do with the immunity. (v.) Able to ward off a particular infection. Alternatively, this term can be used to mean an organism shows no impacts from exposure to a particular poison or process. More generally, the term may signal that something cannot be hurt by a particular drug, disease or chemical.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
infect To spread a disease from one organism to another. This usually involves introducing some sort of disease-causing germ to an individual.
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
infectious An adjective that describes a type of germ that can be transmitted to people, animals or other living things.
mature (adj.) Connoting an adult individual or full-grown and fully developed (non-juvenile) form of something. (verb) To develop toward — or into — a more complex and full-grown form of some individual, be it a plant, animal or microbe.
microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
microcephaly A condition that leaves babies with abnormally small heads and partially developed brains.
mutation (v. mutate) Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.
National Institutes of Health (or NIH) This is the largest biomedical research organization in the world. A part of the U.S. government, it consists of 21 separate institutes — such as the National Cancer Institute and the National Human Genome Research Institute — and six additional centers. Most are located on a 300 acre facility in Bethesda, Md., a campus containing 75 buildings. The institutes employ nearly 6,000 scientists and provide research funding to more than 300,000 additional researchers working at more than 2,500 other institutions around the world.
nerve A long, delicate fiber that transmits signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold or pain.
outbreak The sudden emergence of disease in a population of people or animals. The term may also be applied to the sudden emergence of devastating natural phenomena, such as earthquakes or tornadoes.
Pacific The largest of the world’s five oceans. It separates Asia and Australia to the west from North and South America to the east.
primate The order of mammals that includes humans, apes, monkeys and related animals (such as tarsiers, the Daubentonia and other lemurs).
protein A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
risk The chance or mathematical likelihood that some bad thing might happen. For instance, exposure to radiation poses a risk of cancer. Or the hazard — or peril — itself. (For instance: Among cancer risks that the people faced were radiation and drinking water tainted with arsenic.)
species A group of similar organisms capable of producing offspring that can survive and reproduce.
strain (in biology) Organisms that belong to the same species that share some small but definable characteristics. For example, biologists breed certain strains of mice that may have a particular susceptibility to disease. Certain bacteria or viruses may develop one or more mutations that turn them into a strain that is immune to the ordinarily lethal effect of one or more drugs.
variant A version of something that may come in different forms. (in biology) Members of a species that possess some feature (size, coloration or lifespan, for example) that make them distinct. (in genetics) A gene having a slight mutation that may have left its host species somewhat better adapted for its environment.
virologist A researcher who studies viruses and the diseases they cause.
virus Tiny infectious particles consisting of RNA or DNA surrounded by protein. Viruses can reproduce only by injecting their genetic material into the cells of living creatures. Although scientists frequently refer to viruses as live or dead, in fact no virus is truly alive. It doesn’t eat like animals do, or make its own food the way plants do. It must hijack the cellular machinery of a living cell in order to survive.
Zika A viral disease that can be transmitted to humans via mosquitoes. About 20 percent of infected people get sick. Symptoms include a slight fever, rash and pinkeye and usually fade quickly. A growing body of evidence suggests that the virus could also cause a devastating birth defect — microcephaly. Evidence suggests it may also cause neurological conditions such as Guillain-Barré syndrome.
Journal: L. Yuan et al. A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science. Published online September 28, 2017. doi: 10.1126/science.aam7120.
Journal: Y. Liu et al. Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature. Vol. 545, May 25, 2017, p. 482. doi:10.1038/nature22365.