Can We Better Understand How Zika Leads to Microcephaly? A Systematic Review of the Effects of the Zika Virus on Human Brain Organoids

Abstract

Background: The innovative human brain organoid model represents a unique opportunity to better understand the genesis of congenital brain abnormalities, particularly microcephaly, caused by Zika virus (ZIKV) infection during early pregnancy.

Methods: A systematic review was conducted to investigate how ZIKV leads to microcephaly in a novel experimental model that mimics early brain development. Studies were gathered by searching MEDLINE/Pubmed, LILACS, and LiSSa for reports on effects of ZIKV infection on human brain organoids. From 146 identified papers, 13 articles were selected for review.

Results: This review found that ZIKV of African, Latin American, and Asian lineages caused productive replication after 72 hours, preferentially infected neural progenitor cells over mature neurons, reduced both cell populations, and caused premature differentiation. Limited data involving only African and Latin American lineages showed a reduction in populations of proliferating cells and intermediate cells, and overall decreased viability. Furthermore, all 3 lineages caused heightened apoptosis and reduced organoid size.

Conclusions: This review concludes that, in organoids, ZIKV causes productive replication, infects neural progenitor cells over mature neurons, decreases both populations, causes premature differentiation, induces apoptosis, and reduces size.

Keywords: Zika; microcephaly; neural progenitor cells; organoid.