Brain organoids uncover mechanisms of virus-induced microcephaly
2021
Vienna BioCenter (VBC), Vienna, Austria
Viral infection in early pregnancy is a major cause of microcephaly. However, how distinct viruses impair human brain development remains poorly understood. Here human brain organoids were used to study the mechanisms underlying microcephaly caused by Zika virus (ZIKV) and herpes simplex virus (HSV-1). The authors found that both viruses efficiently replicate in brain organoids and attenuate their growth by causing cell death. However, transcriptional profiling revealed that ZIKV and HSV-1 elicit distinct cellular responses and that HSV-1 uniquely impairs neuroepithelial identity. Furthermore, the authors demonstrated that, although both viruses fail to potently induce the type I interferon (INF) system, the organoid defects caused by their infection can be rescued by distinct type I interferons.
The findings highlighted the distinct paths used by various viruses to cause microcephaly and revealed complex cellular immune defences, such as a neuroprotective role of various type I IFN responses. The importance of these findings also resides in their unique observation in 3D brain organoid cultures, and not in 2D culture systems, thus stressing the superiority of these models in reproducing virus-induced neuropathological conditions and their relevance in studying the mechanisms of viral infections.
Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly
Jürgen A. Knoblich
Added on: 04-15-2021
[1] https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00110-7[2] https://www.oeaw.ac.at/imba/research-highlights/news/brain-organoids-uncover-various-mechanisms-of-virus-induced-microcephaly
