Foundation Independent Investigator led team proving Zika virus causes microcephaly, other birth defects

Foundation Independent Investigator led team proving Zika virus causes microcephaly, other birth defects

Posted: May 17, 2016
Foundation Independent Investigator Led Team Proving Zika Virus Causes Microcephaly, Other Birth Defects

For months, readers of front-page news have been learning of the spread of the Zika virus in Central and South America, and from there, most recently, into the southernmost part of the United States. Carried by common mosquitoes, the virus has roused fear particularly because of its association with major birth defects in children of women infected during pregnancy.

Chief among these is a condition called microcephaly, a serious illness that manifests at birth or in the period following, a cause of intellectual disability, impaired motor function, small head size, and seizures. Zika infection has also been suspected as a cause of Guillain-Barré syndrome, an autoimmune disease that results in severe muscle weakness.

Until this past week, there was no direct evidence of how the Zika virus affects human development – only an increasing body of clinical data powerfully suggesting a linkage of presumed cause and effect. A scientifically proven causal explanation is now in hand, however. 

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Until now, there was no direct evidence of how the Zika virus affects human brain development – only clinical association of maternal infection with birth defects. The causal linkage has now been made, paving the way to development of a vaccine.

On May 11, a multinational team led by 2014 NARSAD Independent Investigator grantee Alysson R. Muotri, Ph.D., of the University of California, San Diego, published a breakthrough paper in the journal Nature. Dr. Muotri and colleagues presented results of experiments demonstrating that infection by the Brazilian strain of the Zika virus, isolated from an infected microcephalic baby, causes growth impairments, including signs of microcephaly, in mice. The team also showed that the virus infects human cortical progenitor cells, leading to an increase in cell death. This is the process that causes microcephaly and possibly other developmental illnesses. 

Progenitor cells in the developing fetal brain that are targeted by Zika are the wellspring of the mature brain. Significant impairment in their maturation is a probable cause of birth defects. “We noticed cortical malformations in the surviving mice [infected with the virus], with reduced cell number and cortical layer thickness, signs associated with microcephaly in humans,” the researchers reported.

The experimental results were widely hailed as pivotal in the development of vaccines to counter or prevent Zika infection. Importantly, the team’s experiments settled any question over how the virus is communicated to the fetus: Dr. Muotri and colleagues showed that it can indeed cross the so-called placental barrier, the protective layer that evolved to protect the developing fetus.

In the Zika work, Dr. Muotri and colleagues made use of advanced methods that enable scientists to grow 3-dimensional spheres of cells from reprogrammed neural progenitor and stem cells. Called neurospheres and cerebral organoids, these spherical agglomerations of cells can be infected with a virus, in this case different strains of Zika, to determine the impact of infection on neural development. 

”Our data reinforce the growing body of evidence linking the Zika outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the effectiveness of therapeutic approaches to counteracting the harmful impact of the virus on human neurodevelopment,” the team said.

 

Foundation Independent Investigator Led Team Proving Zika Virus Causes Microcephaly, Other Birth Defects Tuesday, May 17, 2016

For months, readers of front-page news have been learning of the spread of the Zika virus in Central and South America, and from there, most recently, into the southernmost part of the United States. Carried by common mosquitoes, the virus has roused fear particularly because of its association with major birth defects in children of women infected during pregnancy.

Chief among these is a condition called microcephaly, a serious illness that manifests at birth or in the period following, a cause of intellectual disability, impaired motor function, small head size, and seizures. Zika infection has also been suspected as a cause of Guillain-Barré syndrome, an autoimmune disease that results in severe muscle weakness.

Until this past week, there was no direct evidence of how the Zika virus affects human development – only an increasing body of clinical data powerfully suggesting a linkage of presumed cause and effect. A scientifically proven causal explanation is now in hand, however. 

On May 11, a multinational team led by 2014 NARSAD Independent Investigator grantee Alysson R. Muotri, Ph.D., of the University of California, San Diego, published a breakthrough paper in the journal Nature. Dr. Muotri and colleagues presented results of experiments demonstrating that infection by the Brazilian strain of the Zika virus, isolated from an infected microcephalic baby, causes growth impairments, including signs of microcephaly, in mice. The team also showed that the virus infects human cortical progenitor cells, leading to an increase in cell death. This is the process that causes microcephaly and possibly other developmental illnesses. 

Progenitor cells in the developing fetal brain that are targeted by Zika are the wellspring of the mature brain. Significant impairment in their maturation is a probable cause of birth defects. “We noticed cortical malformations in the surviving mice [infected with the virus], with reduced cell number and cortical layer thickness, signs associated with microcephaly in humans,” the researchers reported.

The experimental results were widely hailed as pivotal in the development of vaccines to counter or prevent Zika infection. Importantly, the team’s experiments settled any question over how the virus is communicated to the fetus: Dr. Muotri and colleagues showed that it can indeed cross the so-called placental barrier, the protective layer that evolved to protect the developing fetus.

In the Zika work, Dr. Muotri and colleagues made use of advanced methods that enable scientists to grow 3-dimensional spheres of cells from reprogrammed neural progenitor and stem cells. Called neurospheres and cerebral organoids, these spherical agglomerations of cells can be infected with a virus, in this case different strains of Zika, to determine the impact of infection on neural development. 

”Our data reinforce the growing body of evidence linking the Zika outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the effectiveness of therapeutic approaches to counteracting the harmful impact of the virus on human neurodevelopment,” the team said.