Fig. 7: Histone code induction in CD14⁺ monocytes following vaccination or NACE2i treatment.

a The nuclear distribution of H3K27ac and H3K4me2 were examined in CD14⁺ PBMCs from pre- and post-vaccination donors either remaining uninfected or subsequently becoming infected. Integral radial pixel intensities for H3K27ac (mean ± SEM) are plotted as a function of distance from the nuclear center and clock-scan analysis. n = 1 individual (2 FOVs analyzed). Two-sided Kolmogorov–Smirnov test. b Dot plot quantification of nuclear fluorescence intensity (NFI) of H3K27ac or H3K4me2 in CD14⁺ PBMCs derived from the samples in (a). n = 7 individuals. One-way ANOVA with Tukey’s post hoc test. c Representative 3D maps of the nuclear density of H3K27ac using the surface plot profile function in ImageJ-Fiji to plot 3D density to demonstrate the nuclear distribution. n = 1 individual. d Nuclear distribution of H3K27ac was examined in CD14⁺ PBMCs (treated with either control or NACE2i) derived from a post-infection cohort: fully vaccinated and recovered from SARS-CoV-2 infection. Integral radial pixel intensities for each histone mark (mean ± SEM) are plotted as a function of distance from the nuclear center and clock-scan analysis. n = 1 individual (2 FOVs analyzed). Two-sided Kolmogorov–Smirnov test. e Dot plot quantification of the NFI of H3K27ac in CD14⁺ PBMCs from PB and PI cohorts: fully vaccinated and recovered from SARS-CoV-2 infection and treated with control or NACE2i. n = 5 individuals/cohort. One-way ANOVA with Tukey’s post hoc test. f Nuclear distribution of H3K27ac examined in ACE2^me+ cells from lung sections of SARS-CoV-2-infected golden Syrian hamsters treated with vehicle control or NACE2i. Integral radial pixel intensities for each histone mark (mean ± SEM) are plotted as a function of distance from the nuclear center using super-resolution images and clock-scan feature of ImageJ-Fiji. n = 5 hamsters/group (1 FOV/animal with ≥ 20 cells analyzed). Two-sided Kolmogorov–Smirnov test. g Representative image of FFPE hamster lung bronchioles infected with SARS-CoV-2 and treated with vehicle or NACE2i (n = 3 hamsters/group). Super-resolution images are shown. FFPE tissues were stained for ACE2^me (yellow), H3K27ac (red), and SARS-CoV-2 spike (green). DAPI (cyan) was used to visualize nuclei. h Graphical overview of epigenetic reprograming in hamster bronchiolar epithelium and human CD14⁺ monocytes.