Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids.

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 ant

SUBMITTER: Rybak-Wolf A 

PROVIDER: S-EPMC10322700 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature