Fig. 7: Perfusion of acyclovir (ACV) through microvascular network inhibits epidermal HSV infection.

a Schematic of HSV epidermal infection and antiviral drug ACV perfusion. b ACV perfusion through the microvasculature at the concentrations of 0, 0.2, or 20 µM, 4 h before the epidermis was infected with HSV-2 (10⁶ PFU). Skin-on-chip was fixed and stained for HSV gene expression 48 h post infection. c ACV perfusion (20 µM) at time points either 24 h prior HSV infection, immediately following infection or 24 h after the epidermis was infected with HSV-1 K26 (10⁶ PFU). Skin-on-chip was fixed and stained 48 h after infection. d HSV infection in the epidermis under ACV perfusion at different concentrations as described in (b). Maximum intensity projection of stacked confocal images. HSV-2 (red), DAPI (blue). Scale bar: 500 µm. e Number of infected cells (*p = 0.0298, ***p = 0.0003) and MFI (**p = 0.0011, ***p = 0.0001) of HSV gene expression in the infected epidermis. Data normalized to untreated control across ACV conditions. n = 3. f HSV infection in the epidermis under ACV perfusion at different time points as described in (c). Maximum intensity projection of stacked confocal images. HSV-1 K26 (green), DAPI (blue). Scale bar: 500 µm. g Levels of GFP expression in epidermal cells infected with HSV-1 K26 with or without ACV perfusion as described in (c). Each dot represents one cell. h Mean GFP fluorescence intensity following HSV infection under various ACV treatment conditions relative to untreated control, n = 3. ***p = 0.003, **p = 0.0046. i Percentage of GFP+ cells in each condition, data were normalized to untreated control, n = 3. ***p = 0.0005, ***p = 0.0007, *p = 0.0117. Statistics generated by repeated measures one-way ANOVA with Tukey’s post-test (indicates difference from control). Data are provided in a Source data file.