SARS-CoV-2 MA10 infection of C57BL/6J mice. Infectious viral particles (A) and viral RNA (B) were quantified in the lung of infected C57BL/6J mice at 2, 4, and 7 dpi. Histological scores (C) and scoring for SARS-CoV-2 antigen abundance (D) in the lung of C57BL/6J mice are shown. Bars represent the mean ± standard deviation. Dotted line represents the limit of detection. Temporal histologic lesions (E to H) and viral antigen abundance and distribution (I to L) in the lung of MA10-infected C57BL/6J mice. At 2 dpi, there was evidence of bronchiolar (F, asterisk) epithelial degeneration and necrosis (F, inset), with abundant viral antigen (J), mild peribronchiolar inflammation, and blood vessels with hypertrophied (activated) endothelium (F, arrow). Similar alterations were noted at 4 dpi (G, inset), but these resolved by 7 dpi (H). Mild interstitial pneumonia was first identified at 4 dpi (G) and persisted until the end of the study (7 dpi) (H). At 4 dpi, viral antigen was rare and only identified within the cytoplasm of scattered pneumocytes (K, arrows). No viral antigen was noted at 7 dpi (L). H&E (E to H) and Fast Red (viral antigen) (I to L); ×200 total magnification. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.