Publikationsdatenbank

Modelling viral encephalitis caused by Herpes simplex virus 1 infection in cerebral organoids (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Rybak-Wolf, Agnieszka

Wyler, Emanuel

Pentimalli, Tancredi Massimo

Legnini, Ivano

Oliveras Martinez, Anna

Glažar, Petar

Loewa, Anna

Kim, Seung Joon

Kaufer, Benedikt (WE 5)

Woehler, Andrew

Landthaler, Markus

Rajewsky, Nikolaus

Quelle

Nature microbiology

Bandzählung: 8

Heftzählung: 7

Seiten: 1252 – 1266

ISSN: 2058-5276

Sprache

Englisch

Verweise

URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/37349587/

DOI: 10.1038/s41564-023-01405-y

Pubmed: 37349587

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.