Zika Virus is a kind of virus which has drawn great attention by many of the researchers worldwide. The growing rate of the spreading of the virus in the new born babies with malformed heads due to microcephaly is causing a serious situation which needs to be looked upon. In addition to this latest research shows that the possible infections by the Zika Virus can cause the damage to the brain cells. Study has also shown that inhibiting the mechanism can also reduce the effect being caused to the brain cells by means of triggering the immune system. It is being hinting a new therapeutic approach which will be mitigating the effects of the prenatal zika virus infection. The research was being funded as a part of the National Institutes of Health grants DA039562 and Al043198.
3D model analysis of brain cells
In case of the 3-D model of analysis, it was being found that Zika Virus is activating the immune receptor named TLR3, which is in turn inhibiting the development of the brain cells and its survival which is being causing the organoids for shrinking – an effect reminiscent of microcephaly. The US center for the Disease Control and Prevention has concluded that the infection by the Zika Virus in the pregnant women can possibly stunt the neonatal development of the brain and is being leading to the bringing of the babies being born with the abnormally smaller heads, condition being known as microcephaly.
For the first time the researchers from the University of California San Diego School of Medicine has determined a way by which the Zika virus can possibly damage the brain cells. The study is being published in the Journal Cell Stem Cell on 6th May, 2016 which is also showing how the inhibiting mechanism can possibly reduce the damage being caused to the brain cell, being hinting at a newer therapeutic approach for mitigation of the effects of the prenatal infection by the Zika Virus. Using the stem-cell based 3D modeling of the first-trimester human brain which has discovered that Zika Virus has activated TLR3 which is molecular human cells which is normally being used for defending against the invading viruses.
Inhibiting the Stem cells for specializing over the brain cells
In turn of the hyper activated TLR3, it is being turning off the genes which the stem cells require for specializing into the brain cells. It is being ultimately triggering the cell suicide. When the researchers inhabited the TLR3, the corresponding damage to the brain cells was being greatly reduced for the organoid model.
Tariq Rana being the senior author of the study, PhD, Professor of pediatrics at UC San Diego School of Medicine commenting over the same says, “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. 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.”
In the study team of Rana made sure that their organoid model truly represent the earlier model of developing human brain. They even found that the model of the stem cell is differentiating into the various cells of the brain in the same way as they do during the first trimester of the human development. The researchers has also compared the patterns of the gene activation for the organoid cells for their database of the human brain genetic information. They even found that their organoid model is being closely resembling to the fetal brain tissue during the eight to nine weeks of the post-conception.
Effect of organoid cells while adding the strain containing Zika Virus
When the prototype of the Zika Virus Strain was being added by the team for the case of 3D brain model, the organoid quite shrank. About five days after the infection, healthy, mock-infected brain organoids has grown to about an average of 22.6 percent. As compared to that the Zika Infected organoids were decreased in size by an average of 16 percent. Team also noted that TLR3 gene was also being activated by means of the Zika-virus-infected organoids . It is a kind of protein which is mostly been found inside and even attached to outside of the cells. It’s main job is to work as an antenna being sensing the double stranded RNA specific to the viruses.
On binding of the viral RNA with the TLR3, it specifically kicks off an immune response which can help in activating many of the different genes for aiding the fight against the infection. However in this particular case researchers found that activation of the TLR3 is also influencing the 41 genes which is being adding up to the double whammy causing the diminished stem cell differentiation over the brain cells and even the increased suicide of the cells. It is a form of the carefully controlled process being named as apoptosis.
Treating the infected cells with Inhibitors
Researchers thought of this as some of the symptoms of microcephaly. When researchers treated them with the TLR3 inhibitors, it greatly impacted the effect of the Zika Virus infection over the health of the brain cells and even the organoid size, being underscoring the TLR3 role being linking the infection and even the cell damage. However, the organoids being treated weren’t perfect. Treated organoids still encountered more cell death and disruption as compared to the healthy organoid cells.
The corresponding study is just yet being conducted in laboratory over the human and mouse cells. The Zika Virus strain which was used in the study (MR766) was originally being originated in Uganda while the current Zika Outbreak in the Latin America is slightly different than the strain which originated in Asia. Rana commenting over the same says, “We used this 3D model of early human brain development to help find one mechanism by which Zika virus causes microcephaly in developing fetuses. 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.”