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These findings have come to light through a study carried out on the fetal brain model which shows that Zika virus damages the growing neonatal brain cells resulting in a condition known as microcephaly in which the head of the fetus is abnormally small.
The exact mechanism by which Zika virus causes microcephaly in the neonates was unknown. This study has, however, answered many of the questions regarding the effects of Zika Virus on normal neonatal brain development.
The study was carried out by researchers at the University Of California San Diego School Of Medicine. The results of the study were subsequently published in Cell Stem Cell. The researchers used a 3D stem cell model of a first-trimester fetal brain.
The organoid model that was used was equivalent of the first trimester human brain in which the stem cells developed into brain cells in the same manner as the actual human brain. The same model was used by the investigators to compare the gene activation in stem cells to the genetic store of the actual human brain.
Zika Virus Invades Human Immune System
The researchers experimented by adding the Zika Virus sample to the organoid brain model. The Zika virus strain that was employed during this study (MR766) first originated in Uganda. As a result, the 3D model was found to shrink. Five days after the introduction of the Zika virus prototype strain, the healthy brain model showed 22.6% growth as compared to the infected organoid which showed merely 16% growth.
The researchers found that Zika virus acts by activating TLR3, a molecule which human cells employ for defense against the viruses and is found both inside and outside the human cells. TLR3 acts a detector for RNA viruses invading the cells.
Activation of TLR3 stimulates a cascade of events during which the excessively stimulated TLR3 switches off the genes that mature into human brain cells and activates the genes that are responsible for apoptosis, programmed cellular death. In this way, the growth of human brain is inhibited. Activation of TLR3 has been found to affect the expression of 41 genes in total.
Going a step further, the researchers stopped the activation of TLR3. They noticed that the damage induced on the human brain was visibly reduced following the inhibition of TLR3.
According to Tariq Rana, professor of pediatrics at UC San Diego School of Medicine and the lead author of the study, Zika Virus affects the human brain development and growth by turning the immune system of the body upon itself.
The Future Prospects
This study has proved to be a milestone for the discovery of the treatment of the Zika virus infection and for the prevention of brain damage. TLR3 inhibitors can be effectively used to prevent neonatal brain damage caused by Zika virus infection in pregnant women. In this way, the chances of microcephaly in neonates can be significantly reduced.
Further studies to understand the precise action of Zika virus in humans and how it affects various organ systems is underway in order to formulate better treatments for its treatment.