Figure 3.
Replication and pathogenicity of BA.2 in K18-hACE2 mice
6- to-8-week-old female and male K18-hACE2 transgenic mice were intranasally inoculated with 5 × 103 plaque-forming units (PFUs) BA.2 or BA.1. Nasal turbinates and lungs of infected mice were collected on 2, 4, or 6 dpi for viral burden determination (n = 4 for BA.2 on 2, 4, and 6 dpi; n = 5 for BA.1 on 2 and 4 dpi; n = 4 for BA.1 on 6 dpi). Brains of infected mice were collected on 6 dpi for viral burden determination (n = 4). Body weight and survival of the infected mice were monitored for 14 days (n = 8).
(A–E) Virological assessment of BA.2- and BA.1-infected K18-hACE2 mice. Subgenomic envelope (sgE) gene expression in nasal turbinates and lungs on 2 and 4 dpi was quantified with probe-specific qRT-PCR (A and B). Infectious viral titers in nasal turbinates and lungs on 2 and 4 dpi were quantified with plaque assays (C and D). SgE gene expression in nasal turbinates, lungs, and brains 6 dpi was quantified with probe-specific qRT-PCR (E).
(F) Representative images of immunohistochemistry staining for detection of N protein (brown) of SARS-CoV-2 in the lungs of infected mice (n = 5 for BA.1, n = 4 for BA.2).
(G) Representative images of hematoxylin and eosin (H&E) staining for detection of pathological changes in the lungs of infected mice (n = 5 for BA.1, n = 4 for BA.2). See also Figure S3.
(H and I) Body weight (H) and survival (I) of K18-hACE2 mice infected with BA.2 or BA.1.
Data represent mean ± SD from the indicated number of biological repeats. Statistical differences were determined with two-way ANOVA (A–D), two-tailed Student’s t test (E and H), or log rank (Mantel-Cox) test (I). Data were obtained from two independent experiments. Four to six sections were taken from each mouse for histology and immunochemistry analysis. Scale bars represent 100 μm. Each data point represents one biological repeat. ∗p < 0.05, ∗∗ p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.