First Full Genome Analysis Solves the Mystery of How Zika Got So Dangerous

Jan 10, 2017 11:40 PM
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The mention of Zika can strike fear in the hearts of pregnant women. With infections increasing around the world, including in the US, researchers are fighting the clock to figure out how the virus can have such horrific effects in some people.

Spread by a bite from the Aedes aegypti mosquito, most Zika infections produce no symptoms or are mild and produce flu-like symptoms of fever, rash, and body aches that resolves within a few days. Some people aren't so lucky, though.

For every 1,000 people infected with Zika, somewhere between 2 and 10 people will develop Guillain-Barré syndrome, a disorder where the body's immune system attacks the nerves. It shows up as weakness and abnormal sensations that spread to the arms and upper body. Some people can experience life-threatening paralysis that interferes with breathing, heart rate, and blood pressure.

Scientists estimate that 11% of women infected with Zika during their first trimester of pregnancy will have a baby with microcephaly—a severely small head, less than 5% of the size of a normal baby's head. Usually, the baby's brain is also abnormally smaller.

These are scary statistics, and being at the mercy of a mosquito bite isn't exactly a reassuring way to try to prevent the infection. Will we ever have a vaccine or an effective way to control the Zika virus? The answer to that may lie in finding out exactly how it wreaks havoc within our cells.

Researchers have looked for the mechanism that allows this virus to be so powerful within the human body—and a team from the University of Maryland School of Medicine have figured it out and published their findings online in the Proceedings of the National Academy of Sciences.

Unraveling the Mechanism of Viral Injury Using Beer Yeast

What has been known about the Zika virus is that it infects nerve cells and affects developing brains by slowing cell growth and development, causing cell abnormalities and cell death. Until this research paper was published, what has not been known is how the virus does this.

The Zika genome is made of a simple strand of the genetic material RNA. Once the virus attaches to and enters the host cells, it releases its RNA and and causes the host cell to produce 14 viral proteins. To determine which of these viral proteins were involved in the cell effects known to be caused by the virus, the team, led by Dr. Richard Zhao, turned to a beer yeast for help.

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Schizosaccharomyces pombe.

The beer yeast, whose scientific name is Schizosaccharomyces pombe, is a type of fission yeast. Fission yeast contain a very small number of genes, making them a simple system to work with, but also contain the same genes responsible for cell division and cellular organization that humans have, making them a relevant system to work with.

Using cloning and functional analysis of the Zika genome, Zhao and his team produced the virus's 14 proteins in the lab. Next, they exposed beer yeast cells to each of the 14 proteins to see how the cells responded.

Two very important findings resulted from the research. The experiments showed that seven of the 14 proteins harmed or damaged the yeast cells—and the team identified exactly which proteins. The researchers also showed how the proteins damaged the cells. Their analyses showed that stopped cell proliferation caused abnormal cell enlargement and triggered oxidative damage in the cells that led to their death.

The team had identified the viral proteins that caused the same type of cell damage that humans experience.

Moving Forward from Beer Yeast to Humans

A press release from the University of Maryland School of Medicine reported that the researchers' next step is to figure out how these seven proteins work in human cells. It will be important to determine if all these proteins are needed to cause cell damage or if some are more damaging than others.

The authors hope that knowing what causes the cellular damage may provide a target for future prevention and treatment of Zika infections.

Cover image by Girish Khera/Wikimedia Commons

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