2023 Author: Bryan Walter | [email protected]. Last modified: 2023-05-21 22:24
Chinese scientists have found a link between Zika virus infection and microcephaly. It turned out that the Zika virus destroys a protein that is responsible for transporting fatty acids into the brain tissue. By feeding infected mice with omega-3 fatty acid, microcephaly can be avoided. The research is published in the journal Science Advances.
The Zika virus is insidious in that it causes unremarkable symptoms that are the same for many fevers. Therefore, many of its carriers do not even notice the disease and do not go to doctors. As a rule, pregnant women find out that it was Zika who settled in their body - when microcephaly is found in their fetus. This is an underdevelopment of the brain, which is accompanied by a decrease in its volume and mental retardation.
Jia Zhou and colleagues at the Chinese Academy of Medical Sciences College of Medicine have traced the link between Zika virus infection and brain damage. They pushed away from an article by their predecessors, who found that a certain mutation causes lethal microcephaly in mice - that is, animals die before birth. This mutation affected the Mfsd2a gene. It encodes a transporter protein that is responsible for the transport of fatty acids from the blood into the cells of the vessel wall. Therefore, Zhou and colleagues suggested that the course of Zika infection may also be related to the work of this protein.
To begin with, the scientists worked with a culture of endothelial cells of cerebral microcapillaries. They measured the amount of the Mfsd2a protein: there was a lot of it in healthy cells, but after they were infected with the Zika virus, it completely disappeared within three days. Other viruses the researchers used as controls - hepatitis C virus and West Nile virus - had no such effect.
Then the researchers decided to find out which of the viral proteins is responsible for the destruction of Mfsd2a. They took another culture - kidney cells - and injected into it simultaneously Mfsd2a and one of the Zika proteins, and then measured the amount of Mfsd2a. It turned out that the coat protein ZIKV E was the culprit in the destruction of the protein. Then the scientists introduced into the cells blockers of different pathways of protein cleavage, and found that only a proteasome blocker could stop the destruction of Mfsd2a. Thus, they found that the envelope protein of the Zika virus marks the Mfsd2a protein for destruction in the proteasome.
Mfsd2a works as a carrier of fatty acids into the cell. Therefore, its destruction should lead to a change in the lipid composition of the cell. The researchers measured the concentration of docosahexaenoic acid (omega-3), an essential fatty acid that cells cannot synthesize on their own, in the brains of healthy and infected mice. It turned out that Zika infection reduces the uptake of fatty acid from the blood, as well as its content in the composition of phospholipids inside the cell.
Then the scientists decided to test what would happen if the level of omega-3 acids in the brain was replenished. They infected newborn mice with Zika virus and then injected them with fatty acid into the abdominal cavity. A few days later, they found that the fatty acid not only saved mice from microcephaly, but also restored the amount of Mfsd2a in the brain cells.
There are two opposite consequences of this discovery. On the one hand, on its basis, it is possible to develop prevention of the development of microcephaly in humans. On the other hand, it provides a tool for regulating blood flow. Another research group recently found that blocking Mfsd2a increases the permeability of the blood-brain barrier. Probably, with the help of the Zika virus, it will be possible to “disassemble” the barrier between the blood and the brain in order to inject, for example, drugs for neurodegenerative diseases there.
Previously, scientists found that the Zika virus attacks human nerve cells at the earliest stages - before implantation, when the actual nerve tissue does not yet exist. And there have already been proposals to use the Zika virus for therapeutic purposes - for example, to fight brain cancer.