Scientists discover how Zika virus disrupts fetal brain development

Fetal biometry, ultrasound and serial fetal brain MR imaging of a ZIKV-infected pregnant pigtail macaque.
Fetal biometry, ultrasound and serial fetal brain MR imaging of a ZIKV-infected pregnant pigtail macaque.

In a recent paper published in Nature Medicine, scientists report how Zika virus disrupts fetal brain development during pregnancy.

More than 30 scientists from University of Washington, Seattle, Washington University School of Medicine, and Seattle Children’s Research Institute worked together to conduct the research.

They are experts in virology, immunology, pediatrics, pathology, radiology, neurology and medicine.

In the paper, researchers describe the development of fetal brain lesions in a pregnant pigtail macaque with Zika viral infection. Pigtail macaques (a type of monkey) are typically found in the rainforests and lowlands in many places of Southeast Asia. They are widely used in psychological studies and medical research.

In the study, researchers inoculated Zika virus in five locations on the forearms of a pregnant pigtail macaque at 119-day gestation (corresponding to 28 weeks of human pregnancy). They wanted to test whether Zika virus could cause fetal brain injury.

The pregnant animal looked healthy and did not develop signs of rash, conjunctivitis of fever. Before the onset of labor at 162-day gestation (corresponding to 38 weeks of human pregnancy), researchers conducted cesarean on the animal.

Before the cesarean, a weekly ultrasound check demonstrated a lag in the growth of the fetal brain diameter. The inflected fetal brain was significantly different from the normal fetal brain in pregnant macaques reported before.

In addition, MRI scan showed that the white matter of the fetal brain stopped growing about 3 weeks after the viral infection. White matter is important for the communication between different brain regions.

Researchers also found that over time, multiple fetal organs, such as liver and placenta, showed similar features to that in humans who had the congenital Zika viral syndrome.

Researchers suggest that Zika virus can cross from the mother via the placenta and into the fetal brain. In addition, the virus level in the fetal brain is higher than that in the mother.

Zika viral infection can cause a loss of brain cells and brain cell connections, a smaller-than-normal hindbrain (a part of the brain that controls motor functions), and a larger-than-normal fluid-containing brain cavities in the brain.

Researchers also suggest that nonhuman primates are ideal for studying infection in pregnancy because these animals most closely mimic gestation in human, including brain development and placentation. Future work will focus on the mechanisms of fetal injury caused by Zika virus.

Citation: Waldorf KMA, et al. (2016). Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate. Nature Medicine, published online. doi: 10.1038/nm.4193.
Figure legend: This image is credited to Waldorf KMA et al.