Zika's viral odyssey finally revealed

TheInstitut de Research en Infectiologie de Montpellier (CNRS/UM) has demonstrated the ability of the Zika virus to adopt the so-called "Trojan horse" strategy to reach the brain of its host. These results are published in the highly select journal Nature Communications.

In 2015, the major Zika epidemic that hit Brazil highlighted the virus's responsibility for the cerebral underdevelopment of babies born to infected mothers, as well as for the onset of neurological damage - encephalitis-like - in adults. Until now, researchers have been unable to understand how the virus migrates into brain tissue. To protect itself, the brain has a cellular barrier, reputed to be impenetrable, ensuring hermetic separation between blood and tissue. Raphaël Gaudin's team at theInstitut de Research en Infectiologie de Montpellier (CNRS/UM) has now solved the mystery. Once again, this work demonstrates that viruses have more than one trick up their sleeve when it comes to achieving their goals.

The "Trojan horse" strategy

Just as Ulysses, hero of the Odyssey, hid his soldiers in a large wooden horse to enable them to enter and assault the city of Troy, the Zika virus has found its own wall-passer in a sub-type of white blood cell. Hiding in what are known as monocytes, the virus will take control of these cells, originally designed to defend our immune system, and force them to migrate to our brain, thus breaching our famous blood-brain barrier.

Zebrafish and mini-brains

To demonstrate this clever ploy, two experiments, in vivo and in vitro, were carried out. First, human monocytes infected with the Zika virus were injected into a zebrafish. This quasi-transparent animal had its blood vessels fluorescentized beforehand, so that the path of the virus could be followed in real time and in 3D. The researchers were thus able to observe that infected cells actually migrated out of the blood vessels and into the tissues much more rapidly than cells not exposed to Zika.

This spinning inside the brain is carried out in vitro. Raphaël Gaudin's team collaborated with a Dutch laboratory specializing in the creation of "mini-brains" produced from embryonic stem cells. These organoids were exposed to infected monocytes, healthy monocytes and free virus. The researchers observed a greater spread of the virus in the brain by the infected monocytes, confirming their hypothesis. A promising discovery that could well become Zika's Achilles heel, opening the way to new therapeutic applications to combat the virus. Unless, of course, the virus still has other myths up its sleeve.

Zika in brief...

The Zika virus was discovered in the Zika forest (Uganda) in 1947. The virus is mainly contracted through the bite of Aedes mosquitoes, sexual transmission and blood transfusions. While Zika-related symptoms are generally harmless in adults, transmission from pregnant women to the fetus can cause severe cerebral malformations in newborns, including microcephaly. In 2016, photographer Felipe Dana put into images the terrible consequences of Zika in northeastern Brazil, a region hard hit by an epidemic.