The reason why Zika virus attacks the developing brain to cause microcephaly has been solved by scientists in Cambridge. Surprisingly, the work may also highlight a new way to tackle aggressive brain tumours.
The 2014 outbreak of Zika virus in Brazil was heralded by a dramatic increase in cases of babies born with microcephaly, a condition characterised by an undersized head and brain. Studies on affected patients confirmed that Zika virus infection during pregnancy was the cause, although why the virus was targeting the nervous system wasn't know.
Now two teams working at Cambridge University, one, a group of geneticists headed by Fanni Gergely and the other virologists led by Ian Goodfellow, have uncovered the answer and may have serendipitously also discovered a means to make much safer Zika vaccines and a treatment for brain cancer.
The insight for their discovery came when Gergely's group were studying some Turkish children with an inherited form of microcephaly. These individuals had a change in a gene called MSI-1 - musashi-1.
Eager to find out what this gene might do, the team searched the genetic database for the target that MSI-1 acts on in cells. It turns out that it controls a constellation of genes that coordinate the behaviour of the cells that go on to form the brain in a developing baby.
More surprising though, is that the Zika virus genetic code also recognises and responds to MSI-1. And because developing brain cells are awash with this factor they probably provide an attractive host to support the growth of the virus.
At this point, Goodfellow's team were able to show that blocking the MSI-1 signal in cultured cells profoundly impairs the growth of Zika virus, which they speculate occurs because the MSI-1 signal helps to stabilise the genetic messages being made by the virus as it grows. And by soaking up the available MSI-1 in the cell, the virus prevents infected cells from following their correct developmental instructions, leading to underdevelopment of the brain and, ultimately, microcephaly.
Although this discovery does not offer a remedy for people already affected by Zika virus infection, there are nonetheless two profound spin-offs.
"We could use this knowledge to make a mutated form of Zika virus that lacks the ability to bind MSI-1," says Goodfellow. "This means we can make a much safer live Zika vaccine that would make a person immune but couldn't harm a developing baby."
At the same time, another project kicking off in Cambridge is seeking to exploit the destructive power of Zika viruses to target one of the most aggressive forms of brain cancer. Neurosurgeon and researcher Harry Bulstrode points out that brain cancers called glioblastomas, which are highly invasive and notoriously hard to treat, arise from a population of stem cells very similar to the cells that form the nervous system in the first place.
"So we think that Zika virus will behave in these cells like it does in the cells of a developing infant's brain, and destroy them." Critically, such a therapy shouldn't harm the surrounding heathly, mature brain tissue, because adult neurones lack "embryonic" factors like MSI-1, so they should be unharmed.
It's early days though. "We're just getting started," says Bulstrode. "We're going to begin with mice carrying human glioblastomas, to establish the treatment model. Then we'll see how it goes..."
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