Zika Definitively Linked To Microcephaly In Mice

Mouse fetuses that were injected with Zika virus and carried to term display the hallmarks of microcephaly.

AsianScientist (May 12, 2016) – Researchers in China have found that mouse fetuses injected with the Asian Zika virus strain and carried to term display the characteristic features of microcephaly. The authors say these findings, published in Cell Stem Cell, are direct evidence that Zika infection causes microcephaly in a mammalian animal model.

The authors believe that their animal model, paired together with global transcriptome datasets of infected brains, will provide valuable resources for further investigation of the underlying cellular and molecular mechanisms of Zika virus, particularly in relation to fetal neural development.

The research was a collaborative effort between co-senior authors, Dr. Xu Zhiheng at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences and Dr. Qin Cheng-Feng at the Beijing Institute of Microbiology and Epidemiology.

In the present study, Zika virus was injected directly into fetal mouse brains. If given too early, the embryos didn’t survive, so the researchers began by looking at the equivalent of the second trimester in humans, when the unborn fetus’ neural progenitor cells are intensively expanding and generating new neurons at the same time.

With this model, they could observe as the brain shrunk corresponding to the increase in viral load and intensity of the immune response. As expected, the virus infected the neural progenitor cells, and the infected brains revealed expression of genes related to viral entry, altered immune response, and cell death.

The mice survived to birth but were eaten by their mothers, which often occurs if pups are noticeably unwell; preventing further observation. To overcome this problem, the researchers plan in future to use lower doses of the Zika virus to see whether that will affect survival. The researchers are also working to identify potential drugs that could reverse the process of Zika virus-induced microcephaly in mice.

“The most surprising part of this study is that it was mostly neural progenitor cells that got infected in the beginning and mostly neurons that became infected at a later stage, five days after injection, when the presence of Zika virus increases several hundred fold,” said Xu.

“However, almost all cell death was found in neurons other than neural progenitor cells. This indicates that neurons, but not neural progenitor cells, are prone to induced cell death by the Zika virus.”

Qin warned that as mice are not humans, caution must be exercised when translating these findings into human disease.


The article can be found at: Li et al. (2016) Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice.

———

Source: Cell Press; Photo: coniferconifer/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Asian Scientist Magazine is an award-winning science and technology magazine that highlights R&D news stories from Asia to a global audience. The magazine is published by Singapore-headquartered Wildtype Media Group.

Related Stories from Asian Scientist