[LUM#12] A strategist named Zika

[LUM Magazine] - Published on May 5, 2020 in Science-Society

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 attack its host's brain. A test-tube version of the myth, revealed bythe Montpellier Institute for Infectious Disease Research and published in the journal Nature Communications.

The brain is a fortress that the human body works to defend from any external intrusion thanks to what is known as the blood-brain barrier. This barrier is composed of an army of cells "connected to each other by junctions so tight that even water or blood cannot pass through," explains Raphaël Gaudin, a virologist atthe Montpellier Infectiology Research Institute. "And a virus is much bigger than a water molecule!"

Trojan horse

And yet, it must be said that some of them have no qualms about invading our skulls. Among these unwanted conquerors is the Zika virus. "This process of Zika transmigration to the brain had already been observed, but its mode of operation remained a mystery to researchers," explains the biologist. Although virologists have been aware of the Trojan horse strategy 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 experiments were conducted. First, human monocytes infected with the Zika virus were injected into zebrafish embryos, a popular animal model in biology due to their near transparency. "We used a genetically modified fish line so that the cells in their blood vessels would express GFP, in other words, turn green, and we tracked the virus's path through the fish's blood vessels in real time and in 3D." The researchers were able to observe an acceleration in the transmigration of infected monocytes to the brain compared to healthy blood cells.

Achilles heel

This research was conducted in vitro. Raphaël Gaudin's team collaborated with a Dutch laboratory specializing in the creation of brain organoids, or "mini-brains" produced from embryonic stem cells. "These organoids were placed under a blood-brain 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 infected monocytes.

This promising discovery could well become Zika's Achilles heel and pave the way for new therapeutic applications to combat the virus, because although it is asymptomatic in adults in 85% of cases, it can very rarely cause 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 brain connections involved in emotional and sexual behavior," 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 have observed that the virus acts inside white blood cells to modify the molecules responsible for adhesion. "When we observe how healthy monocytes and infected monocytes adhere to the cells of the blood vessels into which they want to migrate, we see that the infected monocytes spread out much more. This has enormous implications!"

Understanding this phenomenon could not only inhibit the migration of infected monocytes, but, beyond Zika, "cause 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 then become a new breadcrumb trail in the fight against cancer.

Keywords: LUM#12, LUM Magazine, Medicine, Research, Health