Fig. 4: ACV does not prevent HSV-1-driven inflammatory responses. | Nature Microbiology

Fig. 4: ACV does not prevent HSV-1-driven inflammatory responses.

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

Fig. 4

a, Enriched gene sets for the assessed cell types based on the comparison of HSV-1-infected (1 and 3 dpi) and 3 dpi HSV-1-infected ACV-treated organoids with uninfected organoids. Colour indicates normalized enrichment score (NES) values and dot size represents −log10-adjusted P value for statistically significant pathways according to gene set enrichment analysis (GSEA) analysis. b, UMAP plots of cells coloured by the TNF pathway activity score in each cell and separated in uninfected (CTRL), HSV-1-infected (1 and 3 dpi) and 3 dpi HSV-1-infected ACV-treated organoids, with red and blue indicating increased and decreased scores, respectively. Pooled data from two independent iPS cell lines, n = 2 biological replicates for each line. c, Representative western blot analysis of p-p65 expression in uninfected, 3 dpi HSV-1-infected and 3 dpi HSV-1-infected ACV-treated organoids; GAPDH serves as loading control, and GFP indicates virus expression (bottom). d, Semi-quantification of p-p65 protein expression by densitometry in uninfected, 3 dpi HSV-1-infected and 3 dpi HSV-1-infected ACV-treated organoids, normalized to GAPDH expression. *P < 0.05, **P < 0.01, Benjamini–Hochberg-corrected two-sided t-tests. n = 6 biologically independent samples; that is, six batches of pooled organoids from two iPS cell lines; colour indicates cell line of origin. Bar plots and error bars show mean ± standard error. e, Representative immunohistochemistry for SOX2 (top) and HSV-1–GFP protein expression (middle) in uninfected, HSV-1-infected (1 and 3 dpi), and 3 dpi HSV-1-infected ACV-treated organoids. Bottom: merged images (HSV-1–GFP, white; SOX2, red) co-stained with nuclear marker DAPI (blue). Scale bar, 100 µm. Representative image of three experiments (n = 3 independent organoids/condition/iPS cell line).

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