Thread by @ewyler

Out now! Our study on in-depth analysis of Herpes simplex virus 1 infected brain organoids, led by Agnieszka Rybak-Wolf from the @N_Rajewsky lab @BIMSB_MDC!
biorxiv.org/content/10.110…

– summary in the thread below.

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Question: what can we learn about virus-caused encephalitis and neurodegeneration? We used 60 days Lancaster brain organoids, and applied various sequencing (single-cell, spatial, polyA tail), imaging, and electrophysiology methods.

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HSV-1 infection leads to disruption of the organoid structure, as e.g. shown here by Synapsin I staining. Known features of HSV-1 infection such as ARC upregulation or antisense transcription were recapitulated.

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Firing as determined by high-density multi-electrode measurements shows rapid loss of activity about 20 hours post infection.

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Poly-A tails as measured by FLAM-seq get longer, and polyA site usage is shifting.

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Some cell types are much more susceptible to others, and infection in there can progress much faster.

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Transcriptional changes are generally mild, we however see e.g. consistent upregulation of e.g. TNF alpha signaling. (7/9)

Among other features, upregulation of BC200/BCYRN1 (a relatively small non-coding RNA, shown to be upregulated in Alzheimer's patient), and Stathmin-2 downregulation – but much less pronounced in ∆ICP27 knockout infections.

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Thanks to everybody involved for a fantastic team work, and to @AnnaCliffe1 @NirDrayman @DolkenL @beatesodeik and many others from the Herpes community for feedback!

Further reading e.g.
ncbi.nlm.nih.gov/pmc/articles/P…
pubmed.ncbi.nlm.nih.gov/30787148/