Fig. 3: Delta spike mutations drive enhanced fitness in hACE2-knock-in mice.
From: The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype
a–e hACE2-KI mice (7–16 week-old male, n = 8 mice/virus) were intranasally inoculated with 104.3 TCID50 of Delta or Omicron. a Average relative weight loss after infection (Relative weight loss data from each animal is given in Supplementary Fig. 9). b Viral copies per mL of oropharyngeal swabs or per lung and nose sample (n = 16 mice) quantified using E-gene probe-specific RT–qPCR. c Infectious virus titers from the lung and nose samples (n = 16 mice) determined using TCID50 assays in VeroE6/TMPRSS2 cells. d, e Histopathological score and hematoxylin and eosin staining from Delta- and Omicron-infected lung sections (n = 16 mice) at 2 and 4 dpi. Perivascular and peribronchiolar lymphohistiocytic inflammation are highlighted with an arrow, and the higher magnification represented in the lower panel corresponds to the areas highlighted by a square in the upper panel. Scale bars, 500 (upper panel) and 100 µm (lower panel). Data are mean ± s.d. from the indicated number of biological replicates from a single experiment. The color key in a also applies to b, c and d. Statistical significance was determined using an unpaired two-tailed Student t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. f, g hACE2-KI mice (7–19 week-old female, n = 6 mice/group) were intranasally inoculated with 104 TCID50 of a 1:1 mix of f Delta and Omicron, or g SARS-CoV-2S-Delta and SARS-CoV-2S-Omicron. qPCR quantification of the ratio of the two variants or recombinant viruses present in the inoculum is reported. Oropharyngeal swabs were collected 1 and 2 dpi; lung and nose tissues were collected on 2 dpi. Pie charts show the ratio of variants detected in each sample at the indicated dpi (n = 6 mice/group). Pie chart sizes are proportional to the total number of viral genome copies per ml (swabs) or per sample (tissues), as shown in the legend on the right. Gray pies indicate values below the LOD (i.e., 103 viral RNA copies per mL/sample). Mouse silhouettes are colored to indicate the dominant SARS-CoV-2 variant (>66%) in the last positive swab sample from the corresponding mouse. KI numbers 1–12 denote individual hACE2-KI mice. Data was obtained from one experiment. Source data are provided as a Source Data file 3.
