Zika Virus Shown to Impact Fetal Brain GrowthJune 01, 2016
Researchers at the University of California San Diego School of Medicine have established proof of the Brazilian Zika virus strain deterring fetal brain growth and have come up with a potential method for reducing total damage to developing brain cells.
Organoids, or “mini brains”, were created using 3D, stem-cell based models of a first-trimester human brain to explore Zika’s effects on fetal brains. Through the models, it was discovered that Zika activates a molecule known as TLR3, triggering apoptosis. This resulted in the infected organoids decreasing in size by an average of 16%.
TLR3 is normally responsible for defending human cells from invading viruses. However when hyper-activated, this molecule shuts down genes needed by stem cells to develop into brain cells while prompting cell suicide.
To confirm that the TLR3 activation caused the shrinkage, senior author Tariq Rana, PhD and his team applied TLR3 inhibitors to the infected organoids. “We all have an innate immune system that evolved specifically to fight off viruses, but here the virus turns that very same defense mechanism against us,” said Rana, professor of pediatrics at UC San Diego School of Medicine. “By activating TLR3, the Zika virus blocks genes that tell stem cells to develop into the various parts of the brain. The good news is that we have TLR3 inhibitors that can stop this from happening.”
While the inhibitors showed potential in countering the virus’ influence, it did not halt cell death and disruption completely. In addition, the researchers also cautioned that the experiments only reflected results from human and mouse cells grown in the lab infected with a different Zika strain from the one originating in Asia.
“We used this 3D model of early human brain development to help find one mechanism by which Zika virus causes microcephaly in developing fetuses,” Rana said, “but we anticipate that other researchers will now also use this same scalable, reproducible system to study other aspects of the infection and test potential therapeutics.”
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