abnormally small and underdeveloped brain -- can cause seizures, developmental delays, and intellectual disability.3 Moreover, doctors and scientists have found that many cases also involve enlarged ventricles with excess cerebrospinal fluid that fill the “vacuum” left by damaged areas of the brain. This phenomenon can make fetal skulls appear normally sized early in pregnancy, despite a severe lack of fetal brain tissue.6 Collectively, these brain abnormalities caused by the virus are known as Congenital Zika Syndrome, and scientists have only recently begun to understand many of the underlying mechanisms causing these tragic complications of the Zika virus.8
Researchers at the Johns Hopkins University Medical School recently 3D-printed a miniaturized brain, or organoid, from human stem cells to recreate the precise effects of the Zika virus on the developing fetal brain. According to the Dana Foundation, the simulated brains “exposed to Zika virus for just one day during the earlier stages of growth showed . . . reduced proliferation, as well as increased cell death, of neural stem cells.” The cells also exhibited a slower rate of growth and abnormal cell replication cycles.4 Additionally, the researchers found that Zika did not immediately kill the infected stem cells. The virus used the cells’ machinery and protein-making capacity to replicate itself and spread rapidly, infecting 85% of the cells in a span of three days.7
Furthermore, the Zika virus can also stimulate calcium deposits in the developing brain through a process known as “calcification.” However, this common complication of brain infections occurs in an unusual location: the intersections of the brain’s grey and white matter.1 According to Dr. Catherine Y. Spong from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, this may become a pattern associated with the Zika virus. However, since the grey and white matter intersection heavily controls brain formation, damage to this portion of the brain may suggest that babies appearing unscathed may experience developmental difficulties as they grow.1 The boundary between the grey and white matter portions of the brain are crucial to the differentiation and spatial translocation of developing neurons. Damage to this cortical area would result in scrambled connectivity and messaging, possibly signaling challenges in coordination, memory, and learning for babies affected by the Zika virus.1
To examine the more precise causes of Zika-induced neural damage, researchers at the University of California - San Francisco may offer a clue. Using RNA sequencing, the scientists examined genes expressed in fetal brain tissue.4 Through their analysis, they discovered that a protein called AXL is expressed throughout the developing cerebral cortex, particularly in the “end-feet” of radial glial cells which form parts of capillaries. Since it is known that the Zika virus uses this AXL receptor to infect human skin cells, the investigation of the University of California suggests that this protein may be the primary channel by which Zika gains entry into the fetal brain and disrupts normal development.4
Although the harmful effects of the Zika virus are yet to be mitigated, researchers around the world are racing to create an effective vaccine. For now, pregnant women must avoid mosquito-laden areas to reduce the risk of Zika infection and avert the crippling complication that may occur. As the epidemic continues around the world, the global health community must unite not only to discover a cure for the Zika virus, but also to prevent other obscure pathogens from emerging from their damp, dark dens and devastating future generations.