New York: Researchers have discovered how hijacking a human immune molecule the Zika virus infection in pregnant women can stunt neonatal brain development, leading to babies born with abnormally small heads — a condition known as microcephaly.
Using a 3D, stem cell-based model of a first-trimester human brain, the team discovered that Zika activates TLR3, a molecule human cells normally use to defend against invading viruses.
In turn, hyper-activated TLR3 turns off genes that stem cells need to specialise into brain cells and turns on genes that trigger cell suicide. When the researchers inhibited TLR3, brain cell damage was reduced.
“We all have an innate immune system that evolved specifically to fight off viruses, but here the virus turns that very same defence mechanism against us,” said senior study author Tariq Rana, professor of pediatrics at University of California, 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,” he explained.
The study, published in the journal Cell Stem Cell, also showed that inhibiting this mechanism reduces brain cell damage, hinting at a new therapeutic approach to mitigate the effects of prenatal Zika virus infection.
“The good news is that we have TLR3 inhibitors that can stop this from happening,” Rana pointed out.
This new research has been conducted only in human and mouse cells growing in the laboratory thus far.
In addition, the Zika virus strain used in this study (MR766) originated in Uganda, while the current Zika outbreak in Latin America involves a slightly different strain that originated 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 foetuses, 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,” Rana added.