Skip to Content
Merck
  • Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids.

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

Nature microbiology (2023-06-23)
Agnieszka Rybak-Wolf, Emanuel Wyler, Tancredi Massimo Pentimalli, Ivano Legnini, Anna Oliveras Martinez, Petar Glažar, Anna Loewa, Seung Joon Kim, Benedikt B Kaufer, Andrew Woehler, Markus Landthaler, Nikolaus Rajewsky
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Sox2 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-GAPDH antibody, Mouse monoclonal, clone GAPDH-71.1, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Green Fluorescent Protein (GFP) antibody, Mouse monoclonal, clone GSN149, purified from hybridoma cell culture
Sigma-Aldrich
Anti-β-Tubulin III antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-NeuN Antibody, clone A60, clone A60, Chemicon®, from mouse
Sigma-Aldrich
Anti-MAP2 Antibody, clone AP20, Alexa Fluor 555 Conjugate, clone AP20, from mouse, ALEXA FLUOR 555