Figure 1.
SARS-CoV-2 Infection in Conventional Laboratory Strains of Mice and Expression of hACE2 after AdV Transduction
(A and B) 3-to-4-week-old BALB/c, DBA/2J, Stat1−/− C57BL/6, Rag1−/− C57BL/6, and AG129 mice were inoculated via combined intranasal and intravenous routes with 105 focus-forming units (FFU) of SARS-CoV-2. Weight change (A) was monitored, and viral burden (B) in the lung was determined at 10 dpi by RT-qPCR and expressed as copies of viral N gene per mg of tissue (n = 2 to 3 for each strain). Naive mice are shown as a control. Error bars indicate standard deviations (SD).
(C) HEK293 cells were transduced with AdV-hACE2-GFP. Flow cytometric analysis of hACE2 and GFP expression was analyzed at 4 and 10 h after AdV transduction. One of two experiments is shown.
(D) mRNA expression levels of hACE2 in the lungs of mice receiving the AdV-hACE2 at D-3, D-1, D0, and D4 relative to SARS-CoV-2 infection (2, 4, 5, and 8 days after AdV delivery) via intranasal route as measured by species-specific qRT-PCR of hACE2. Bars indicate median values.
(E) In situ hybridization using probes for hACE2 in lungs of control mice receiving anti-Ifnar1 mAb (left) or at D-3, D-1, and D0 relative to SARS-CoV-2 infection (2, 4, or 5 days post-transduction of mice receiving anti-Ifnar1 + AdV-hACE2) (right). Images show low-power (top; scale bars, 100 μm) and medium-power (middle [blue] and bottom [red]; scale bars, 100 μm) magnifications with an additional high-power magnification inset (scale bars, 10 μm). Arrows indicate hACE2-positive cells in medium-power magnification (representative images from n = 3 per group).