Study may have found link between Zika virus and microcephaly in babies
Doctors at three US universities infect lab-grown human stem cells with virus and discover 90 per cent of one type of brain cell are quickly hijacked to make copies of it. Their findings could be used to identify potential therapies
A team of researchers suspect they have discovered how the Zika virus probably causes microcephaly in fetuses. The virus selectively infects cells that form the brain’s cortex, or outer layer, making them more likely to die and less likely to divide normally and make new brain cells.
They say their experiments also suggest the highly susceptible lab-grown human stem cells they used could be employed to screen for drugs that protect the cells or ease existing infections.
“Studies of fetuses and babies with the telltale small brains and heads of microcephaly in Zika-affected areas have found abnormalities in the cortex, and Zika virus has been found in the fetal tissue,” said Dr Guo-li Ming, a professor of neurology, neuroscience, and psychiatry and behavioural science at the Institute for Cell Engineering at Johns Hopkins University in the United States. “While this study doesn’t definitely prove that Zika virus causes microcephaly, it’s very telling that the cells that form the cortex are potentially susceptible to the virus, and their growth could be disrupted by the virus.”
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In 2015, the Zika virus began spreading throughout the Americas and a potential link was seen between the virus and a significant increase in cases of fetal microcephaly, as well as other neurological abnormalities. This connection and the proliferation in cases led to the World Health Organisation declaring Zika virus an international public health emergency.
Ming led the research team along with Dr Hongjun Song, a professor of neurology and neuroscience at the institute, and Dr Hengli Tang, a virologist at Florida State University in the US.
Results of the experiments, conducted by researchers at Johns Hopkins, Florida State University, and Emory University, also in the US, are described online in the journal Cell Stem Cell.
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In a quickly executed study that reflects the global public health threat posed by Zika, the researchers compared its effect on cells known as cortical neural progenitor cells to two other cell types: induced pluripotent stem cells and immature neurons. Induced pluripotent stem cells are made by reprogramming mature cells, and can give rise to any cell type in the body, including cortical neural progenitor cells. Cortical neural progenitor cells in turn give rise to immature neurons.
The experiments, conducted in less than a month, began when Tang reached out to Ming and Song, who use stem cells to study early brain development. The Johns Hopkins labs sent team members and cells to Tang’s lab, where the cells were exposed to Zika virus. Then the cells’ genetic expression – evidence of which genes were being used by the cells and which weren’t – were analysed in Peng Jin’s laboratory at Emory University.
According to Tang, three days after exposure to the virus, 90 per cent of the cortical neural progenitor cells were infected, and had been hijacked to churn out new copies of the virus. Furthermore, the genes needed to fight viruses had still not been switched on, which is highly unusual. Many of the infected cells died, and others showed disrupted expression of genes that control cell division, indicating that new cells could not be made effectively.
Using specific, known types of cells allowed the researchers to see where the developing brain is most vulnerable, Song says. He and Ming are now using the cells to find out more about the effects of Zika infection on the developing cortex. “Now that we know cortical neural progenitor cells are the vulnerable cells, they can likely also be used to quickly screen potential new therapies for effectiveness,” Song adds.
Zika virus has recently emerged as a public health concern, but it was first discovered in Uganda in the 1940s. Since then, small outbreaks have appeared in Asia and Africa, but symptoms were generally mild and did not appear to have any long-term effects. Carried by infected Aedes aegypti mosquitoes, Zika is largely transmitted through bites, but can also occur through intrauterine infection or sexual transmission.