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Experiments show link between Zika and fetal brain damage

March 4, 2016

PARIS — Scientists said Friday they had found the first evidence of a biological link between the Zika virus sweeping Latin America and microcephaly, a severe deformation of the brain among newborns.

Laboratory tests found that the virus targeted key cells involved in brain development and then destroyed or disabled them, they said.

The findings are the first concrete evidence of a link between the mosquito-borne virus and microcephaly, which until now had been circumstantial, said Guo-li Ming, a professor of neurology at Johns Hopkins’ Institute for Cell Engineering, and a co-leader of the research.

“Studies of fetuses and babies with the telltale small brains and heads of microcephaly in Zika-affected areas have found abnormalities in the cortex, and Zika virus has been found in the fetal tissue,” he said in a statement.

Scientist exposed three types of human cells in a lab dish to the Zika virus, a method called in-vitro experiment.

The first — known as human neural progenitor cells (hNPCs) — is crucial for the development of the cortex, or outer layer, of fetal brains.

Damage to these cells, which eventually differentiate into mature neurons, would be consistent with the brain defects caused by microcephaly.

The other two types of cells were stem cells and neurons.

As predicted, Zika virus attacked the human neural progenitor cells. Within three days of exposure, 90 percent were infected, and nearly a third had died.

Infected cells, meanwhile, had been hijacked to turn out new copies of the virus.

Furthermore, the genes needed to fight viruses failed to activate, which was a highly unusual outcome.

By comparison, the other two types of human cells were relatively unharmed.

“Our results clearly demonstrate that Zika can directly infect hNPCs in vitro with high efficiency,” the study concluded.

“It is very telling that the cells that form the cortex are potentially susceptible to the virus,” Ming added.

The findings, published in the journal Cell Stem Cell, may help to identify drugs that protect these vulnerable cells or reduce infections after they occur.

“Now that we know cortical neural progenitor cells are the vulnerable cells, they can likely also be used to quickly screen potential new therapies,” said co-author Hongjun Song, also from the Institute for Cell Engineering, based in Baltimore, Maryland.

By itself, Zika is typically no more threatening than a bad cold or a mild case of the flu. Sometimes there are no symptoms at all.

But the rapidly expanding virus — present in nearly four dozen countries, according to the World Health Organization (WHO) — was suspected of causing microcephaly and other severe conditions.

Last month, Brazil — the country hardest hit by the Zika epidemic — reported 583 confirmed cases of babies with the irreversible birth defect since October 2015, four times the previous annual average.

On Friday, researchers in Colombia reported the country’s first cases of Zika-linked birth defects, according to the Nature science group’s news service.

Scientists not involved in the research welcomed the findings.

“This is exactly the kind of research that we need to demonstrate a causative link and mechanism between the Zika virus and microcephaly,” said Alyssa Stephenson-Famy, an assistant professor of obstetrics and gynaecology at the University of Washington in Seattle.

Mark Schleiss, director of the division of infectious disease and immunology at the University of Minnesota, described the research as a “big step in the right direction.”

“Most scientists have not had any doubt that the Zika virus is responsible for the brain injury,” he noted.

Need to explore link

But he and other experts said many questions remain.

Results from cells in a lab dish may not applicable to patients — “in vivo” in scientific terms.

“This study is just the beginning, and many more studies are needed to understand the relationship between Zika and microcephaly,” commented Amelia Pinto, a professor of molecular microbiology and immunology at Saint Louis University.

“Ultimately, in vivo studies will be needed to confirm a central role of progenitors in bridging virus infection and microcephaly,” said Sika Zheng, a professor of biomedical sciences at the University of California in Riverside.

A study published earlier this week provided similarly solid evidence of that Zika can also cause a rare syndrome, called Guillain-Barre, which attacks the nervous system.

Zika is spread among humans by the Aedes aegypti mosquito, which is found in 130 nations. But recent evidence suggests that it can also be sexually transmitted by men carrying the virus.

See also: 

Costa Rica decrees emergency to prevent spread of Zika, other mosquito-borne viruses

Tourism sector seeks to calm fears of Zika virus

US details cases of 9 pregnant women with Zika virus

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