Scientists confirm for the first time that "Zika" kills developing brain cells

Release date: 2016-03-08

A pregnant woman in Rio de Janeiro, Brazil, gave birth to a baby with a small head after infection with Zika virus.

The fear of Zika virus spreads as quickly as the pathogen itself. For the first time, two laboratory studies provide conclusive evidence of how this virus causes brain defects in infants. Studies have shown that Zika virus can preferentially kill developing brain cells. This finding provides a possible pathological explanation for the association between Zika virus and neonatal small head disease, and will help to explore targeted treatments for Zika infection.

Previous observations suggest that there appears to be some correlation between the rapid spread of the virus in Latin America and the increasing incidence of local small head disease, a birth defect that the brain cannot grow normally. Work done by two research teams independently showed that Zika virus is easily infected with neural stem cells (precursors of nerve cells and other brain cells), whether these cells are in cell culture dishes or called "brain-like" Growing in a three-dimensional mini brain.

Madeline Lancaster, a developmental biologist at the Molecular Biology Laboratory at the Cambridge Medical Research Council in the United Kingdom, said the study was "very important." The result "is very much in line with the characteristics of the baby with a small head that you see."

Zika virus was first discovered in a jungle in Uganda, Africa decades ago. It usually only causes mild symptoms in the human body, including fever and rash. But since the virus began spreading in northeastern Brazil last year, local doctors have noticed a significant increase in the incidence of microcephaly in newborn babies. Many mothers reported that they experienced symptoms consistent with Zika virus infection during pregnancy. However, it is difficult for scientists to prove the link between the virus and birth defects because the blood test for Zika virus is accurate only one week after infection.

However, indirect evidence is accumulating. Researchers have discovered Zika virus in the amniotic fluid of pregnant women with a small head disease, which is also present in the brain tissue of the sick fetus. But because scientists have only conducted very limited research on this virus before, they lack sufficient data to prove how Zika virus can cause small head disease in infants.

To determine the possible effects of the virus on brain development, researchers at Johns Hopkins University in Baltimore, Maryland, and Florida State University in Tallahassee, USA, used induced pluripotent (iPS) cells to grow in culture dishes. Immature brain cells - human cerebral cortical neural progenitors. They then exposed these neural precursor cells to a laboratory strain of Zika virus.

Neuroscientists Hongjun Song and Guo-li Ming, together with virologist Hengli Tang and their colleagues, reported in the March 4 issue of Cell-Stem Cells that Zika virus is very susceptible to infection of these neural stem cells.

The researchers found that 85% of the cells in the dish were infected after 3 days of exposure to the virus. In contrast, when Zika virus was applied to fetal kidney cells, embryonic stem cells, and undifferentiated iPS cells, the infection rate was 10% less after 3 days than the former. The researchers also noted that immature nerve cells derived from neural precursor cells also had a lower infection rate - after 3 days of exposure to the virus, the infection rate was 65%.

The researchers pointed out that the infected neural precursor cells were not killed immediately. Song said that in fact, these viruses use the cellular mechanism to "hijack these cells" for self-replication. He said that this helps the virus spread quickly in the cell population. His research team also reported that infected cells grew very slowly and interrupted the cell division cycle, which is also beneficial for the pathogenesis of microcephaly.

The researchers stressed that after stem cells are infected with Zika virus, there will be some stem cell apoptosis, but they can not directly prove that these stem cells will cause microcephaly after apoptosis.

In the second study, scientists found that Zika virus could interfere with the growth of another neural stem cell type. In a preprinted study published online March 2, Patricia Garcez, a neuroscientist at the D'Or School of Research and Education in Rio de Janeiro, Brazil, and stem cell researcher Stevens Rehen report that they are in a cluster of neural stem cells called neurospheres, and miniatures. The human iPS cells are cultivated in the version of the three-dimensional brain. When the researchers infected these growing cells with Zika virus isolated from a Brazilian patient, the virus quickly killed most of the neurospheres and caused the remaining few surviving cells to be small and deformed. The researchers found that the size of the infected brain was less than half the normal size.

At present, the main concern of Zika virus is that it may cause neonatal small head disease, but it has not been proved that there is a direct relationship between the two. The researchers said that they will study the effects of Zika virus on the brain and the cytological mechanism, molecular mechanism and pathological mechanism of Zika virus infection, and screen the therapeutic drugs on this basis.

The Zika virus was first isolated in the rhesus monkeys of Zika Forest in Uganda in 1947. Historically, the virus has been distributed in the narrow equatorial regions of Africa and Asia. For decades, this virus transmitted by Aedes mosquitoes mainly infects monkeys and occasionally infects humans, but the symptoms are mild. The vector of Zika virus is mainly Aedes aegypti in the tropics, which is the same as mosquitoes that transmit dengue fever, Chikungunya fever and yellow fever. In 2007, the Zika virus spread for the first time across the geographical distribution to the Pacific islands of the Federated States of Micronesia. From 2013 to 2014, other Pacific island countries reported four Zika epidemic cases.

Source: Chinese Journal of Science

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