Figure 4. Increased sensitivity of hCD147KI-NSG and hACE2-NSG mice to SARS-CoV-2 viral infection compared to WT-NSG littermates.

(A) Average body weight loss as a percent of original body weight in WT-NSG, hCD147KI^het-NSG, and hACE2KI^homo-NSG mice following intranasal infection with the TCID50 dose of SARS-CoV-2 virus (1 × 10⁵ PFU in 25 μL per nostril). Error bars represent standard error measure (SEM). (B) Quantification of total SARS-CoV-2 viral copies in the lungs of infected mice at day 2 post-infection by qRT-PCR, as represented by total N-gene RNA copies per lung lobe (left) and by N-gene log-2 fold-change relative to WT-NSG mice (right). Mean values (red) are listed above each group. Each data point represents the average of two duplicate qRT-PCR assays from one mouse lung RNA preparation. (C) Representative sm-FISH images at 20X (first 3 columns) and 63X (4^th column, zoom on region of interest along with Differential Interference Contrast (DIC) overlay) magnifications showing SARS-CoV-2 RNA detection in lung sections from WT (top), hCD147KI^het (middle), and hACE2KI^homo (bottom) mice, seven days post-infection. Blue: DAPI; green: SARS-CoV-2 RNA. Scale bar represents 50 μm. N=5 in WT-NSG, n=3 in hCD147KI^het and n=4 in hACE2KI^homo mice. Statistical significance was determined using an unpaired one-tailed t test. * indicates significance for comparisons between hACE2KI^homo-NSG and WT-NSG mice and # indicates significance for comparisons between hCD147KI^het-NSG and WT-NSG mice where number of symbols indicates significance strength (* or #, p<0.05; ** or ##, p<0.01).