How Zika in pregnancy infects foetus brain
New York, May 12: A team of US researchers has for the first time shown how Zika virus infection in pregnancy can affect foetal brain development.
The findings provide a basis for development of Zika vaccines and treatments, and to study the biology of Zika virus infection in pregnancy.
The researchers from Washington University's School of Medicine developed two mouse models of Zika virus infection in pregnancy and weakened its immune systems before infecting them with the virus.
The findings showed that the deadly virus migrated from the pregnant mouse's bloodstream into the placenta, where it multiplied, then spread into the foetal circulation, thus infecting the brains of the developing pups.
"This is the first demonstration in an animal model of in utero transmission of Zika virus, and it shows some of the same outcomes we've been seeing in women and infants," said Michael Diamond, professor.
Both mouse models reflected some of the key aspects of Zika infection in humans.
"This could be used in vaccine trials, to find out whether vaccinating the mother can protect against uterine infection," Diamond added in the paper published in the journal Cell.
However, microcephaly -- a disease marked by abnormally small heads and the most striking result of human infection - was not observed in either model.
This may be due to differences in how mouse and human brains develop, the researchers said.
In addition, the results showed that the virus in the placenta to be at 1,000 times the concentration in the maternal blood, suggesting that it had not just migrated to the placenta, but multiplied there.
In both models, the virus also was detected in the foetal brain. The researchers observed cell death in the brains of infected foetuses, but there were no obvious abnormalities in the overall structure of the brain.
In one of the experiments, the genetically modified mice lacked a molecule that plays a key role in the immune response to viral infections and thus led to the death of most of the foetuses. The remaining foetuses appeared much smaller than the normal size.
Further, the placentas showed damage. They were shrunken, with a reduced number of blood vessels and were found unable to supply enough oxygen and nutrients to the developing foetus.
They also caused abnormally slow foetal growth and, in severe cases, foetal death.
In another model, they injected mice with antibodies against the same molecule and the effect of Zika infection was found to be less severe. The foetuses survived, although some were smaller than normal.