A strategist named Zika

What do Ulysses and the Zika virus have in common? Cunning! Like the hero of the Odyssey, Zika uses the "Trojan horse" strategy to deceive and assault its host's brain. A test-tube version of this myth, unveiled by theMontpellier Infectious Diseases Research Institute and published in the journal Nature Communications.

The brain is a fortress that the human body defends from outside intrusion by means of what is known as the blood-brain barrier. This barrier is made up of an army of cells "linked together by extremely tight junctions, to the point where not even water or blood can pass through," explains Raphaël Gaudin, virologist at theMontpellier Infectious Diseases Research Institute. And a virus is a lot bigger than a molecule of water!

Trojan horse

And yet, we have to admit that some of them have no qualms about invading our craniums. Among these unwanted conquerors is the Zika virus. " This process of Zika transmigration to the brain had already been observed, but its modus operandi remained a mystery to researchers", explains the biologist. While the Trojan horse strategy has been known to virologists since the 1980s, Raphaël Gaudin and his team were the first to test this scenario in vivo on Zika and a subtype of white blood cells called monocytes.

Two types of experiment were carried out. Human monocytes infected with the Zika virus were first injected into zebrafish embryos, an animal model popular in biology for its near-transparency. "We used a line of fish genetically modified so that the cells in their blood vessels express GFP, in other words, so that they turn green, and we followed, in real time and in 3D, the path of the virus in the fish's vessels". The researchers were thus able to observe an acceleration in the transmigration of infected monocytes towards the brain, compared with healthy cells.

Achilles heel

The rest of the spinning was done in vitro. Raphaël Gaudin's team collaborated with a Dutch laboratory specializing in the creation of cerebral organoids, "mini-brains" produced from embryonic stem cells. " These organoids were placed under a blood-brain cell barrier, over which we introduced infected monocytes, healthy monocytes and free virus. Once again, the researchers observed greater dissemination of the virus in the brain by the infected monocytes.

A promising discovery that could well become Zika's Achilles' heel, opening the way to new therapeutic applications to combat the virus, which is asymptomatic in adults in 85% of cases, but can very rarely be the cause of Guillain-Barré syndrome or even severe encephalitis. " More recently, a study has indicated that the virus may be responsible, in monkeys, for certain alterations in the cerebral connections involved in emotional and sexual behaviour," adds the researcher.

A breadcrumb trail against cancer?

Raphaël Gaudin's team is now focusing on understanding the mechanisms involved in Zika infection of monocytes. The researchers found that the virus acts inside the white blood cell to modify the molecules responsible for adhesion. "When you look at how a healthy monocyte and an infected monocyte adhere to the blood vessel cells they want to migrate into, you see that the infected monocyte spreads out much more. That implies a lot!

Understanding this phenomenon could make it possible not only to inhibit the migration of infected monocytes, but, beyond Zika, to "induce monocyte migration when necessary ", enthuses Raphaël Gaudin. Better still, we could understand and perhaps act on the phenomenon of metastasis migration! The study of Zika would thus become a new Ariadne's thread in the fight against cancer.