Using 3D models of the human brain, researchers have found that the Zika virus turns the immune system against the body.
Step by step, researchers have a better understanding of how the Zika virus can cause microcephaly. This congenital malformation is not observed in all children born to infected mothers: the risk is 1% when the woman is infected during her first trimester of pregnancy.
But until today scientists were unaware of the mechanisms that allow the virus to disrupt the brain development of fetuses. Work published last March showed that it preferentially infects neuronal stem cells and induces their death. One more step has just been taken by an American team from the University of San Diego (California, United States). They publish their work in Cell Stem Cell.
The virus hacks the immune system
Using 3D cell cultures that mimic a “mini-brain,” equivalent to that of a 3-month-old fetus, the researchers found that the Zika virus activates a molecule called TLR3. Usually, the latter is produced by cells to protect against infection. However, when it is “overactive”, TLR3 blocks the genes that allow stem cells to become neuronal cells and activates those that trigger their death. So, when the 3D model was infected with the Zika virus, the researchers noted a decrease in its volume of about 16%.
“We all have immune systems designed to fight off all viruses, but the Zika virus uses these defense mechanisms against us,” says Tariq Rana, professor of pediatrics at the University of San Diego School of Medicine. . By activating TLR3, the Zika virus inactivates genes that induce the differentiation of stem cells in different parts of the brain. But the good news is that we have TLR3 inhibitors that can prevent this process. “
The scientists therefore tested these molecules on the 3D model. They then discovered that these inhibitors considerably attenuated the damage caused by the Zika virus. This result confirms that TLR3 is a key player in the occurrence of microcephaly.
Persistent damage
However, the organoids infected with Zika and treated with these inhibitors were not perfect. These lab brains exhibited developmental abnormalities, in part linked to the destruction of neuronal stem cells.
Although this work is encouraging and opens up a therapeutic avenue, the authors indicate that their experiments were carried out with a viral strain originating in Uganda. However, the strain that is currently rife is Asian. The differences between these two viruses, in particular genetic, would partly explain why such an epidemic could have occurred and the dangerousness of the infection. It could therefore be that the mechanisms used by the current virus are different.
.
