Researchers from the Johns Hopkins University School of Medicine in Maryland recently engaged state-of-the-art biological techniques to delve into the mechanisms behind the Zika virus’ mode of attack in the fetal brain.
The Zika virus is big news. Transmitted by the mosquito and causing only mild symptoms in adults, its effect on the unborn child can be devastating.
Zika has been shown to induce microcephaly in infants – a condition characterized by a particularly small head and brain. The virus also appears to be able to cause other brain abnormalities.
Medical science is scrambling to get a handle on the way in which the virus interacts with fetal tissue in the hope that some kind of defense against its advance can be created.
A research group, led by Guo-li Ming and Hongjun Song, used an ingenious method to uncover fresh information about how Zika makes these severe changes to the developing brain.
Previous work by the Hopkins team helped demonstrate that Zika virus infection is linked to the death of neural stem cells.
However, as the authors were quick to mention, the initial research was carried out in 2D tissue culture and therefore could have missed certain aspects of normal brain development.
For the latest research, Ming and Song used organoids, which are, in effect, mini-brains. They can be grown in a lab and survive for 100 days. They have been used for years, but they also come with inherent problems.
Organoids can be incredibly useful for medical researchers, but they are prohibitively expensive, putting them out of reach for most labs; they also have complex protocols attached, making controlled experiments difficult to conduct.
The researchers managed to circumvent these difficulties by 3D-printing miniaturized spinning bioreactors, which could then be used to produce a high number of organoids from human stem cells. These bioreactors allowed the researchers to examine Zika in developing neural tissue in the most life-like situation to date.
Song, who directs the Stem Cell Program at John Hopkins Medicine Institute for Cell Engineering, says:
“When the Zika crisis came up, we saw that we have the perfect system to study the impacts of the virus.”
The team’s mini-bioreactors were able to produce three types of neural tissue – forebrain, midbrain and hypothalamus – capable of surviving up to 100 days. This gave the team enough time to monitor brain activity as it developed over the equivalent time span of early and mid-pregnancy.
Their findings replicated their previous research; they confirmed that Zika prefers to infect neural stem cells and that the first trimester is the period of time when the brain is at most risk. Ming, a professor of neurology, noted that:
“The organoids are much smaller, and they’re not generating neurons efficiently when they are infected with the Zika virus.”
Infection of fully grown neurons certainly did occur, but the Zika virus preferentially attacked the young, developing neurons, even in the later stages of growth. This lines up well with the results from their earlier 2D investigations.
The results themselves are important as an addition to the overall understanding of the way Zika works; the findings also underline the usefulness of this innovative technique in future research. As Song says:
“With the bioreactor, the model now has power as a preclinical testing ground for potential therapies.”
The research is published this week in Cell; the authors are making the technology available to the scientific community. The team is currently testing FDA-approved compounds on the organoids in the hope that one might have an impact on the Zika virus.
Because Zika’s neural effects are a new area of research and also a rapidly developing and incredibly serious public health issue, researchers are notching up the intensity of the hunt for solutions. Medical News Today recently covered research linking Zika to another brain disorder.