Chinese researchers find direct evidence that Zika causes microcephaly in mice

WASHINGTON -- Chinese researchers said Wednesday they have found direct evidence that Zika infection causes microcephaly, a birth defect marked by an abnormally small head, in mouse experiments.

Mouse fetuses injected with the Zika virus and carried to term within their pregnant mothers display the characteristic features of microcephaly, they reported in the US journal Cell Stem Cell.

As expected, the virus infected the neural progenitor cells, and infected brains revealed expression of genes related to viral entry, altered immune response, and cell death.

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

"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 folds," 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."

In the study, the Zika virus was injected directly into fetal mouse brains, and the researchers found that the embryos won't survive until it was given on the 13.5th day of pregnancy.

Total gestational period in the mouse is about 20 days long, so the time is equivalent of the second trimester in humans, when the fetus's neural progenitor cells are intensively expanding and generating new neurons at the same time, they said.

One problem they encountered was all the infected pups who survived to birth were eaten by their mothers.

"This indicates that the pups were too sick," said Xu. "We have to use lower dose of Zika infection in the future to determine whether the pups will survive longer in order to determinate the long-term consequences of Zika infection on brain development."