As Fear of Zika virus spread almost as quickly as the pathogen itself, two new laboratory studies provide the first strong evidence for how it could cause brain defects in babies: the virus appears to preferentially kill cells of the developing brain. The observation reinforces the case more and more for a connection between the virus, which is spreading rapidly throughout Latin America, and an increased number of cases of microcephaly, a birth defect in which the brain fails to develop properly. The new work, performed independently by two groups, indicating that the virus infects cells easily neural stem precursors to neurons and other brain cells if they are grown on cell culture plates or coaxed to form minibrains 3D brain called organelles.
work "will be very important," said Madeline Lancaster, a developmental biologist who studies human brain development in molecular biology research laboratory in Cambridge Medical Council, UK results "are all in line with what you see babies with microcephaly. "
Zika virus, named after a forest in Uganda where there are first isolated decades, usually causes only mild symptoms in people including fever and rash. But after the virus began spreading in northern Brazil last year, the doctors, he noticed a striking increase in the number of babies born with microcephaly. most mothers reported symptoms consistent with Zika infection during their pregnancy. But it has been difficult to prove a link between the virus and birth defects because blood tests for Zika virus are accurate for about a week after 'infection.
However, circumstantial evidence has accumulated. The researchers identified the virus in the amniotic fluid of pregnant women whose fetuses were diagnosed with microcephaly and also in the brain tissue of a fetus diagnosed with the disease. But because researchers have researched little about the virus before this year, they had little data to suggest how the virus could cause such damage.
To evaluate the possible effects of the virus on brain development, researchers from Johns Hopkins University in Baltimore, Maryland, and Florida State University in Tallahassee he used stem (iPS) cells induced pluripotent cells to develop in laboratory dishes, the immature brain cells called progenitor human neural cortex. (IPS cells are adult cells that have been reprogrammed into stem cells that can develop into most tissues in the body.) They then exposed neural progenitor cells in a laboratory strain of virus Zika.
The virus easily infected neural stem cells, neuroscientists Hongjun Song and Guo-li Ming, virologist Hengli Tang and their colleagues report today in Cell Stem Cell. Three days after the virus has been applied, 85% of the cells in culture dishes were infected. However, when the virus was applied to the fetal cell cultures of kidney, embryonic stem cells and undifferentiated iPS cells were infected within 10% of the cells by day 3. The immature neurons derived from neural progenitors are also less sensitive to the virus; 3 days after receiving a dose of the virus, less than 20% of these cells were infected.
The researchers found that progenitor cells infected are not killed immediately. Instead, the virus "hijacked cells," using the cellular machinery to replicate, said Song. This allowed the virus to spread rapidly through the cell population, he said. His team also reported that the infected cells grew more slowly and disrupted cell division cycles, which could also contribute to microcephaly.
In a separate set of experiments, other researchers found that the virus can hinder the growth of another type of neural stem cells. In a preprint posted March 2, neuroscientist Patricia Garcez and stem cell researcher at the Stevens Rehen D'Or Institute for Research and Education in Rio de Janeiro, Brazil, report more human iPS cells in clusters of neural stem cells called neurospheres, as well as 3D organelles that in some ways resemble a miniature version of the human brain. When they infected the cells with growth isolated Zika of a Brazilian patient, the virus quickly killed most of neurospheres and left the few survivors and misshapen. organelles infected grew at less than half of their normal size.
Lancaster said the findings echo previous studies of genetic mutations that cause microcephaly, which also affect neural progenitor cells. "You have two very different causes of microcephaly, but you know something is happening very similar: a depletion of neural stem cells, and that would lead to fewer neurons" in the brain development, she said
Many questions. on the Zika virus and its apparent link with birth defects remain unanswered. both Garcez Song and say they are now repeating their experience with other viruses, including dengue, a virus closely related to Zika prevailing in the regions currently affected by the epidemic. (Some scientists suspect that prior exposure to other viruses might affect the outcome of Zika infections.) the researchers also still need to understand how the virus crosses placenta and infects the fetus directly, that most viruses can not do.
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