Fig. 9: Gene drive spread during latent infection in C57Bl/6 mice.
From: Viral gene drive spread during herpes simplex virus 1 infection in mice
C57Bl/6 mice were infected with 106 PFU of HSV1-WT on both eyes after corneal scarification. Four weeks later, mice were superinfected with 107 PFU of GD or GD-ns on both eyes, after corneal scarification. After another four weeks, latent HSV-1 was reactivated three times, two weeks apart, with JQ1 and Buparlisib. n = 26 for GD, n = 18 for GD-ns. a Titer and number of shedding events in eye swabs on days 1–3 following JQ1 treatment, by qPCR. Shedding events from the same mouse are connected by a line. b Genotyping of positive eye swabs, detecting mCherry, YFP and CFP markers. Light red indicates low mCherry levels, less than 5% of the total swab titer. Swab genotypes were assessed by ddPCR and confirmed by qPCR for low-titer swabs. Details are shown in Supplementary Fig. 14. c Number and proportion of TG and mice with detectable CFP marker from GD/GD-ns. d, e Latent viral load and proportion in the TG. n = 52 for GD, n = 36 for GD-ns. Black lines indicate the median. f mCherry as a function of CFP. Data was fitted either to the best possible line or to the identity line, and the fits were compared using the extra sum-of-squares F test. GD datapoints were significantly higher than the identity line (p < 0.0001), suggesting gene drive propagation in the TG. Same data as panel (d), excluding non-detected samples. n = 38 for GD, n = 23 for GD-ns. g Log2 fold-change between the proportion of latent mCherry and CFP, using data from panel (e). Samples with low levels of less than 0.5% were excluded. Black lines show the average. Asterisks summarize the results of two-sided Welch’s t-test (p = 0.0053). n = 33 for GD, n = 20 for GD-ns. Titers are expressed in log-transformed copies per swab, or per million cells after normalization with mouse RPP30. n.d.: non-detected. Source data are provided as a Source Data file.
