Extended Data Fig. 8: Brain responses in SARS-CoV-2-infected K18-hACE2 mice at 4 DPI following LNP-CasRx-pre-gCtsl treatment.
From: Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection
a, Schematic illustration of the experimental design. The treatments and virus challenge are same as in Fig. 5a. Brains were collected at 4 DPI for analysis. The right lobes were subjected to RT-PCR, whereas the left lobes were sectioned for staining. b, Viral N gene transcript level. c, Viral E gene transcript level. d, Representative photomicrographs of N-protein immunostaining show strong intracytoplasmic immunoreactivity of neurons in the cerebral cortex and the thalamus and hypothalamus regions of SARS-CoV-2 infected mice. Two sections of brain tissues per mouse from 4 mice of each group (3 for eLNPs group) were subjected to IHC analysis. The occurrence of strong positive staining was indicated in brackets for each group. e, Cxcl10, Ccl2 and Ccl5 transcript levels. b, c, e, all transcript levels were normalized to Gapdh. P values were calculated by one-tailed Mann-Whitney U test, grand mean. NS, not significant. As boxed in the graphs, 5 out of 11 mice in the control group express high transcript levels of viral N gene, E gene and chemokines in the brain. f, Representative photomicrographs of perivascular lymphoid infiltrate (thin arrows) in meninges and Virchow-Robin spaces (thick arrow) show vascular inflammatory changes in all virus-infected groups. Two brain sections per mouse for all mice were subjected to histological analysis and one representative image from each group was shown.
