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| Item Type: | Preprint |
|---|---|
| Title: | Neurodegeneration in human brain organoids infected with herpes simplex virus type 1 |
| Creators Name: | Rybak-Wolf, A., Wyler, E., Legnini, I., Loewa, A., Glažar, P., Kim, S.J., Pentimalli, T.M., Oliveras Martinez, A., Beyersdorf, B., Woehler, A., Landthaler, M. and Rajewsky, N. |
| Abstract: | Herpes simplex virus type 1 (HSV-1) infection of the nervous system may lead to brain damage, including neurodegeneration. However, lack of suitable experimental models hinders understanding molecular mechanisms and cell-type-specific responses triggered by HSV-1. Here, we infected human brain organoids with HSV-1. Known features of HSV-1 infection such as alteration of neuronal electrophysiology and induction of antisense transcription were confirmed. Full-length mRNA-sequencing revealed aberrant 3’ end formation and poly(A)-tail lengthening. Single-cell RNA-seq and spatial transcriptomics uncovered changes in the cellular composition of the infected organoids caused by viral replication and dysregulation of molecular pathways in cell-type specific manner. Furthermore, hallmarks of early neurodegeneration were observed, namely extracellular matrix disruption, STMN2 and TARDBP/TDP43 downregulation, and upregulation of the AD-related non-coding RNA BC200/BCYRN1. These hallmarks were weaker/absent when infecting with a mutant HSV-1 control. Together, our data indicate that brain organoids serve as a powerful model to study mechanisms of HSV-1-driven neurodegeneration. |
| Keywords: | Herpes Simplex Virus Type 1, HSV-1, Brain Organoids, Single-Cell RNA-seq, Neurodegeneration |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2021.03.05.434122 |
| Date: | 7 March 2021 |
| Official Publication: | https://doi.org/10.1101/2021.03.05.434122 |
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