Neurodevelopmental model of Zika may provide rapid answers

Chick embryo a useful model to study effects of Zika partly because of its significant similarity to human fetal development.

A newly published study from researchers working in collaboration with the Regenerative Bioscience Center (RBC) at the University of Georgia demonstrates fetal death and brain damage in early chick embryos similar to microcephaly — a rare birth defect linked to the Zika virus that is now alarming health experts worldwide.

The team, led by Forrest Goodfellow, a graduate student in the University of Georgia College of Agricultural & Environmental Sciences, developed a neurodevelopmental chick model that could mimic the effects of Zika on first-trimester development. Historically, chick embryos have been used extensively as a model for human biology.

Early last spring, Goodfellow began inoculating chick embryos with a virus strain originally sourced from the Zika outbreak's epicenter.

"We wanted a complete animal model, close to that of a human, which would recapitulate the microcephaly phenotype," said Goodfellow, who recently presented the findings at the Southern Translational Education & Research Conference.

The RBC team — which included Melinda Brindley, an assistant professor of virology in the University of Georgia College of Veterinary Medicine, and Qun Zhao, associate professor of physics in the Franklin College of Arts & Sciences — suggested that the chick embryo provides a useful model to study the effects of Zika, in part because of its significant similarity to human fetal neurodevelopment and rapid embryonic process.

"Now, we can look quickly at greater numbers and more closely at a multitude of different strains and possibly identify the critical window of susceptibility for Zika virus-induced birth defects," Brindley said. "With this approach, we can continue to further design and test therapeutic efficacy."

The challenge today is processing and producing therapeutic antibodies in preparation for unpredictable disease outbreaks. Having an active pathogen threat like Zika that can jump across continents reinforces the need for therapeutic innovation.

Early-stage chick embryos are readily available and low in cost, Goodfellow explained. Development within the egg (in ovo) provides an environment that can be easily accessed by high-speed automation. Poultry automation in the Southeast is impressive, and the industry is now using robotic technology, Goodfellow said.

"With egg injection automation and embryo viability technology, we could test tens of thousands of potential therapeutic compounds in a single day," he said.

Since 2011, under the mentorship of Steven Stice, a Georgia Research Alliance eminent scholar and RBC director, Goodfellow has worked extensively with eggs and chickens. In a previous project with Stice and Zhao, the team developed a unique approach of marrying stem cell biology and magnetic resonance imaging (MRI) to track and label neural stem cells.

"We knew we could look at the brain structure, shape and size with MRI, but what we captured was evidence that the infection caused MRI-visible damage, and the total brain volume was substantially smaller," said Stice, faculty lead and principal investigator of the study. "From this finding, our data provide a rationale for targeting future therapeutic compounds in treating early-stage microcephaly to stop or slow the progress of the disease."

The study, "Zika Virus Induced Mortality & Microcephaly in Chicken Embryos," is available online.

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