Could Zika’s link to microcephaly be in the neural stem cells?

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microcephaly

The virus appears to infect a type of neural stem cell that is involved in the development of the brain’s cerebral cortex, says research published in Cell Stem Cell.
[zika microcephaly]
Scientists are exploring how Zika might be linked to microcephaly.

The World Health Organization (WHO) recently declared the Zika virus a Public Health Emergency of International Concern. Zika is now reported to be circulating in 26 countries and territories in Latin America and the Caribbean.

Infection may cause only mild symptoms, or none at all, but the virus has been linked to fetal and newborn microcephaly and serious neurological complications such as Guillain Barré syndrome (GBS).

While the exact workings of Zika remain a mystery, some case reports have indicated that parts of the developing brain progress normally after infection, but that the cortical structures are missing.

Researchers from Johns Hopkins University School of Medicine in Baltimore, MD, and Florida State University joined a team from the Emory University School of Medicine in Atlanta, GA, to conduct the month-long study, which focused on neuronal cells derived from human-induced stem cells.

Rapid spread of infection through cortical neural precursor cells

As the virus normally passes to humans through a mosquito bite, the researchers grew a stock of Zika virus in mosquito cells for a few days. They then applied the virus to human stem cells, known as cortical neural precursors.

These stem cells became havens, or “factories,” for viral reproduction, causing cell death and/or disruption of cell growth. From a single infection, it took just 3 days for the virus particles to spread through a plate of stem cells.

The team found no evidence of antiviral responses in the stem cells, so it remains unclear whether the virus is being cleared from the precursor cells, and if so, how.

The researchers say we need to know whether the virus specifically targets the neural progenitor that is mostly responsible for generating the cortex.

Urgent need for answers

Other questions that researchers are looking for answers to include:

  • Why are the symptoms in adults so mild?
  • How is the virus entering the nervous system of the developing fetus?
  • How is the virus crossing the blood-brain barrier once it enters the blood?
  • Could Zika infect the small population of neural stem cells that, in adults, reside above the brain stem in the hippocampus?

First author Hengli Tang, a virologist whose lab studies RNA viruses such as Zika, Dengue, and hepatitis C, says the team is “trying to fill the knowledge gap between the infection and potential neurological defects.”

Song, a neuroscientist and stem cell biologist, says:

“This is a first step, and there’s a lot more that needs to be done. What we show is that the Zika virus infects neuronal cells in dish that are counterparts to those that form the cortex during human brain development.”

What happens in the developing fetus is still a mystery. The current findings suggest disruption during brain development, but the researchers believe that only clinical studies will provide direct evidence for a link between the Zika virus and microcephaly.

While not proving a direct link between Zika and microcephaly, the present study does pinpoint where the virus may be causing the most damage.

In the near future, the team hopes to grow mini-brains from the stem cells to enable them to track the long-term effects of Zika on neural tissue and, potentially, to start looking for therapeutics.


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