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Washington University researchers use mice to help fight Zika

Zika virus, here shown as a digitally-colorized transmission electron micrograph, can be transmitted by mosquitoes or sexually.
Cynthia Goldsmith | Centers for Disease Control
Zika virus, here shown as a digitally-colorized transmission electron micrograph, can be transmitted by mosquitoes or sexually.

A research team at the Washington University School of Medicine in St. Louis is using genetically modified mice to be able to test possible vaccines and treatments against the Zika virus.

In a study published Tuesday, lead author and professor of medicine Dr. Michael Diamond explained that by infecting these manipulated mice, the researchers were able to mimic how Zika infects humans. That will help scientists understand how the virus works.

“As the Zika virus epidemic emerged, it was clear that we needed to be able to understand fundamental aspects of biology and create models for vaccine and therapeutic testing,” he said. “So having a model, we can use this to rapidly test some areas of either prevention or treatment.”

Zika can be spread by mosquito bites and sexual transmission. It causes relatively minor symptoms like fever, rash and conjunctivitis. However, the Centers for Disease Control and Prevention reports that if a pregnant woman contracts the virus, it can cause microcephaly in fetuses, resulting in small heads and brain damage.

The most recent outbreak of Zika has been concentrated in Central and South America, but previously was reported in Africa, Southeast Asia and the Pacific Islands. The CDC reports local mosquitoes are responsible for almost 350 cases in Puerto Rico, the U.S. Virgin Islands and American Samoa. 312 Americans have contracted Zika while traveling to outbreak areas.

“It was a relatively obscure virus that didn’t cause a severe clinical syndrome – obviously, that’s changed,” said Diamond, an expert in flaviviruses, such as Zika, West Nile and dengue.

The CDC has issued precautions for pregnant women not to travel to areas with Zika virus.
Credit Centers for Disease Control and Prevention
The CDC has issued precautions for pregnant women not to travel to areas with Zika virus.

The Wash U mouse model for Zika is among the first to be developed since research done in the 1970s. Earlier models inserted the virus directly to the brain, but this new model infects the mice through the skin, in the same way a mosquito bite spreads the virus in humans.

To create the model, researchers in Diamond’s lab removed the mice’s genes that create interferon, which helps mouse immune systems to stay relatively resistant to Zika. The scientists were then able to see “where does the virus go and what cells does it infect” in the manipulated mice.

“When we put Zika into some of those mice, we were able to get high levels of infection,” Diamond said. “The virus went to places it does in human patients.”

That includes the central nervous system (the brain and spine) as well as the testes, confirming clinical data that it is “transmitted sexually as well as by mosquito transmission,” he said.

Diamond said he hopes this model will help researchers replicate in mice how the virus is transmitted in utero to fetuses, and ultimately, to baby mice. Understanding how the virus works and how it is transmitted will be keys to fighting the virus.

“Now you have a way to test efficacy of future vaccines or future therapeutics, whether those therapeutics are drugs that exist already that could be used in a different way for a different purpose, or new classes of drugs such as antibody-based therapeutics that would be more specifically against Zika,” Diamond said.

His lab has been working on the mouse model since June, and accelerated its efforts over the last few months. The next area of research is creating antibodies in the lab, he said, as well as developing possible vaccines.

“Do they show efficacy or protective activity, if we transfer them to the mice, either prior to or after Zika infection? Can we mitigate disease by transferring these antibodies?” he said. “Can we actually show that vaccines work against Zika virus, which classes of vaccines? And can we make sure that those vaccines are safe and don’t cause any problems?”

Research – and creating treatments – takes time, but Diamond said his research group is not alone in studying the virus and potential vaccines. He said progress is being made on nearly a “daily basis.”

“Because this is a collective effort internationally, we’re making significant progress,” he said. “There is a global research effort to try to really address this as quickly as possible. We are cautiously optimistic that we are making progress, but it does take time.”

The study was published in Cell Host & Microbe