The results could help develop drugs that reverse this anomaly, which is insufficient development of the skull often accompanied by cerebral atrophy.
USA/CHINA – The global emergency that arose after the spread of zika virus has made countries around the world join forces to improve knowledge about the consequences of the virus. Two studies recently published in Cell show in an experiment conducted in female mice how zika virus is able to cross the placenta and infect the fetus causing microcephaly – insufficient development of the skull in their offspring.
The first study, led by researchers at the University of Washington (USA), establishes the first models on how the zika virus is transmitted from a pregnant mouse to the fetus. The results show how the virus invades and damages the placenta first, and then infect the fetus.
Michael Diamond, one of the scientists involved in this study, said that there were doubts about intrauterine transmission of zika virus. Their data now confirm that the virus crosses the placenta and can cause congenital problems, including fetal death.
Although mice are normally not susceptible to the virus, the researchers developed two models based on a mouse immune to zika virus to provide a path of more accessible entrance. In the first model, female rodents were genetically engineered to have a defective immune system. In the second, the mice received injections of an antibody that prevented the overall performance of their immune system.
In genetically immunodeficient mice, the viral load was 1,000 times higher in the placenta than in maternal serum, indicating the zika virus primarily infects the liver.
Once in the placenta, the virus begins to spread in trophoblast cells, found in embryo, nourish the blood capillaries and damage the fetus. “Previous studies have already shown that cells of the placenta in late stage were resistant to zika infection, our study now shows that the virus is able to cross the barrier between maternal and fetal tissue,” said the researcher.
Most fetuses died before birth and those who survived were born smaller and presented zika replications in the brain and central nervous system.
“Both models provide different aspects of biology,” says Michael Diamond. “In the genetic model we see that this virus slows growth, damages the brain and causes fetal death. The model with antibodies, which is less severe, helps to follow the development of the disease after birth,” the researcher said.
Cause of microcephaly
These results fit with the second study, carried out by the Chinese Institute of Genetics and Developmental Biology and the Institute of Microbiology and Epidemiology, Beijing (China), which shows that the offspring of mice infected with the virus suffer from microcephaly at birth.
In this case, the virus was injected directly into the brains of fetuses in the time when neural progenitor cells intensively expand and neurons begin to emerge.
The scientists were able to observe a reduction in the brain of the offspring with viral load. “The amazing thing about this study is that although both neural stem cells and neurons were infected, most of cell death focuses on the latter, indicating that neurons are more prone to virus-induced cell death” said the author Zhiheng Xu.
“Most often, the placenta is an effective barrier between the mother and fetus, but zika is able to overcome it and spreading various layers of the trophoblast. We see the virus in the lining of blood vessels of a fetus, then circulating and soon after is able to go to the brain,” said Indira Mysorekar, one of the authors from the first study.
Researchers from both studies are still studying and working models to identify potential drugs that can reverse the process of microcephaly caused by zika. But they insist that mice are not humans and that “we must be careful when extrapolating these results to the human model,” concluded Cheng-Feng Qin, the Institute of Microbiology and Epidemiology in Beijing.
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