The Viral Odyssey of Zika Finally Revealed
The Montpellier Institute for Research (CNRS/UM) has demonstrated the Zika virus’s ability to employ a “Trojan horse” strategy to reach its host’s brain. The findings were published in the highly selective journal Nature Communications.
In 2015, the major Zika outbreak that struck Brazil highlighted the virus’s role in the underdevelopment of the brains of babies born to infected mothers, as well as in the onset of neurological disorders—such as encephalitis—in adults. This migration of the virus into brain tissue had previously been poorly understood by researchers. The brain, in fact, has a cellular barrier—considered impenetrable—that ensures a hermetic separation between blood and tissue. The mystery has now been solved thanks to Raphaël Gaudin’s team atthe Montpellier Institute of Research (CNRS/UM). This research demonstrates, once again, that viruses certainly have more than one trick up their sleeves to achieve their goals.
The so-called “Trojan horse” strategy
Just as Odysseus, the hero of *The Odyssey*, hid his soldiers inside a giant wooden horse to sneak them into the city of Troy and attack it, the Zika virus has found its own way in through a specific type of white blood cell. Hidden within what are known as monocytes, the virus takes control of these cells—which are initially designed to support our immune defense—and forces them to migrate to our brain, thereby bypassing our famous blood-brain barrier.
Zebrafish and “mini-brains”
To demonstrate this ingenious strategy, two experiments— one in vivo and one in vitro—were conducted. Human monocytes infected with the Zika virus were first injected into a zebrafish—a nearly transparent animal whose blood vessels had been made fluorescent beforehand—in order to track the virus’s path in real time and in 3D. The researchers were thus able to observe that the infected cells did indeed migrate out of the blood vessels and head toward the tissues much more quickly than cells not exposed to Zika.
Further investigation of this spread within the brain was conducted in vitro. Raphaël Gaudin’s team collaborated with a Dutch laboratory specializing in the creation of “mini-brains” derived from embryonic stem cells. These organoids were exposed to infected monocytes, as well as healthy monocytes and free virus. The researchers then observed greater dissemination of the virus within the brain by the infected monocytes, thereby confirming their hypothesis. This promising discovery could well become Zika’s Achilles’ heel and pave the way for new therapeutic applications to combat the virus—unless the virus has yet more tricks up its sleeve.
Zika at a glance…
The Zika virus was discovered in the Zika Forest (Uganda) in 1947. The virus is primarily transmitted through the bite of an Aedes mosquito, or through sexual contact and blood transfusions. While Zika symptoms are generally mild in adults, transmission from a pregnant woman to her fetus can cause severe brain malformations in newborns, including microcephaly. In 2016, photographer Felipe Dana documented the devastating consequences of Zika in northeastern Brazil, a region hit particularly hard by the epidemic.