Zika Virus Reduced Growth and Induces Cell Death in Human Minibrains

Brazilian researchers from the D’Or Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) have demonstrated the harmful effects of ZIKA virus (ZIKV) in human neural stem cells, neurospheres and brain organoids. Since ZIKV has been gradually established as a direct cause of central nervous system malformations, this study help to elucidate the etiological nature of the recently increasing number of microcephaly cases in Brazil.

Scientists headed by Dr. Stevens Rehen differentiated human induced pluripotent stem (iPS) cells into neural stem cells and into further complex tridimensional structures, known as neurospheres and brain organoids. Neurospheres and brain organoids represent excellent models to investigate developmental neuropathologies, as they can outline, in vitro, several characteristics of the fetal brain formation.

In the present study conducted at IDOR in conjunction with UFRJ, the research team observed that ZIKV infects human-derived iPS neural cells, neurospheres and cerebral organoids causing cell death, malformations and reducing growth by 40%. The researchers also compared these results with the ones generated with Dengue Virus (DENV2). Even though DENV2 infected the cells such as ZIKV, there were no damaging outcomes registered to the neural cells, neurospheres or organoids.

Image shows neural progenitor cells infected with Zika.

Confocal microscopy image of cultured neural progenitor cells infected with ZIKA virus (red). Cell nuclei are seen in blue. Credit: D’Or Institute for Research and Education (IDOR).

Dr. Patricia Garcez, Assistant Professor at UFRJ and first author of the work, point out that “these unique results may unravel some key features of ZIKV infection in the developing brain”.

About this Zika virus research

Source: Stevens Rehen – D’Or Institute for Research and Education
Image Source: The image is credited to D’Or Institute for Research and Education (IDOR).
Original Research: Abstract for “Zika virus impairs growth in human neurospheres and brain organoids” by Patricia P. Garcez, Erick Correia Loiola, Rodrigo Madeiro da Costa, Luiza M. Higa, Pablo Trindade, Rodrigo Delvecchio, Juliana Minardi Nascimento, Rodrigo Brindeiro, Amilcar Tanuri, and Stevens K. Rehen in Science. Published online April 10 2016 doi:10.1126/science.aaf6116


Abstract

Zika virus impairs growth in human neurospheres and brain organoids

Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased significantly in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. Here, we examine the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we show that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development.

“Zika virus impairs growth in human neurospheres and brain organoids” by Patricia P. Garcez, Erick Correia Loiola, Rodrigo Madeiro da Costa, Luiza M. Higa, Pablo Trindade, Rodrigo Delvecchio, Juliana Minardi Nascimento, Rodrigo Brindeiro, Amilcar Tanuri, and Stevens K. Rehen in Science. Published online April 10 2016 doi:10.1126/science.aaf6116

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