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@ARTICLE{RybakWolf:277076,
author = {A. Rybak-Wolf and E. Wyler and T. M. Pentimalli and I.
Legnini and A. Oliveras Martinez and P. Glažar and A. Loewa
and S. J. Kim and B. B. Kaufer and A. Woehler and M.
Landthaler and N. Rajewsky$^*$},
title = {{M}odelling viral encephalitis caused by herpes simplex
virus 1 infection in cerebral organoids.},
journal = {Nature microbiology},
volume = {8},
number = {7},
issn = {2058-5276},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2023-01260},
pages = {1252-1266},
year = {2023},
note = {2023 Jul;8(7):1252-1266},
abstract = {Herpes simplex encephalitis is a life-threatening disease
of the central nervous system caused by herpes simplex
viruses (HSVs). Following standard of care with antiviral
acyclovir treatment, most patients still experience various
neurological sequelae. Here we characterize HSV-1 infection
of human brain organoids by combining single-cell RNA
sequencing, electrophysiology and immunostaining. We
observed strong perturbations of tissue integrity, neuronal
function and cellular transcriptomes. Under acyclovir
treatment viral replication was stopped, but did not prevent
HSV-1-driven defects such as damage of neuronal processes
and neuroepithelium. Unbiased analysis of pathways
deregulated upon infection revealed tumour necrosis factor
activation as a potential causal factor. Combination of
anti-inflammatory drugs such as necrostatin-1 or bardoxolone
methyl with antiviral treatment prevented the damages caused
by infection, indicating that tuning the inflammatory
response in acute infection may improve current therapeutic
strategies.},
cin = {BE01},
ddc = {570},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37349587},
doi = {10.1038/s41564-023-01405-y},
url = {https://inrepo02.dkfz.de/record/277076},
}