How Zika virus causes microcephaly studied

microcephaly  - CDC

Zika virus infection in models that mimics the first trimester of brain development may result in severe damage. – Image : CDC

Researchers have now produced evidence of how Zika virus causes brain defects in babies. Several cases of microcephaly, a rare birth defect in which the brain fails to grow properly, continue to be reported in Brazil following the unprecedented epidemic of Zika virus, which was first detected in the country in May 2015.

Though an association between Zika virus infection and microcephaly has been found, researchers have not been able to prove the link between virus infection and birth defect.

To study how the virus causes birth defects in babies, the researchers from the Federal University of Rio de Janeiro, Brazil used human induced pluripotent stem (iPS) cells to make neural stem cells (NSC), neurospheres and brain organoids.

How quickly the neural stem cells get infected with Zika virus became clear when the researchers detected Zika virus in the cells just 24 hours after they were exposed to the virus.


Human neural stem cell culture infected with Zika virus (red). Cell nuclei are shown in blue. — Photo: Erick Loiola, PhD and Rodrigo Madeiro, PhD – IDOR

The researchers used the Zika virus infected neural cells and cultured them as neurospheres (a culture system composed of free-floating clusters of neural stem cells). While those cells that were not infected with Zika virus generated normal neurospheres, the Zika virus-infected neural cells generated neurospheres with abnormalities. At the end of six days, the virus killed most of the neurospheres, while hundreds of neurospheres grew in the control arm.

To further investigate the impact of Zika virus infection during neurogenesis, organoids were exposed to Zika virus and followed for 11 days. Ptaricia P. Garcez, the first author of a paper published today (April 11) in the journal Science from the Federal University of Rio de Janeiro, Brazil, and others found that the virus reduced the growth of infected organoids by 40 per cent compared with brain organoids under control conditions.

To check if dengue virus, a flavivirus with similarities to Zika virus, caused similar effect on neurogensis, the researchers infected human neural stem cells with dengue virus 2 (DENV2).   After six days, significant differences in cell viability were seen between dengue infected calls and Zika virus-infected neural stem cells. The dengue infected cells were similar to the normal cells and there was no reduction in growth of dengue virus-infected organoids at the end of 11 days.

“These results suggest that the deleterious consequences of ZIKV infection in human neural stem cells, neurospheres and brain organoids are not a general feature of the flavivirus family,” they write.

“Our results demonstrate that ZIKV induces cell death in human iPS-derived neural stem cells, disrupts the formation of neurospheres and reduces the growth of organoids, indicating that ZIKV infection in models that mimics the first trimester of brain development may result in severe damage,” they stress. However, further studies are needed to characterize the consequences of ZIKV infection during different stages of foetal development.

Published in The Hindu on April 11, 2016