Fig. 3: The role of ARF1 in SARS-CoV-2 infection and pathogenicity in vivo.
a–d ARF1 KD inhibits SARS-CoV-2 infection in K18-hACE2 transgenic mice. K18-hACE2 mice were transduced with the viral vectors encoding control or mARF1-targeting shRNAs (5 × 107 transduction units, 100 μL) via intravenous injection, followed by SARS-CoV-2 (500 TCID50, 50 μL) infection through intranasal inoculation at 7 d post-transduction. Five days post infection (dpi), mice were sacrificed for analyses of the ARF1 mRNA levels (a) or infectious virion titers (b) in the lungs by plaque assays or the protein production by WB (c) and IHC (d). Data are presented as means ± SD (a) or median with interquartile range (b), n = 5 mice/group. Statistical significance was determined by two-tailed Student’s t-test (a) or Mann–Whitney U-test (b). **p < 0.01. Representative IHC analyses using the anti-N antibody identified SARS-CoV-2-infected cells in the lung tissue sections (d). e ARF1-KD mice exhibited ameliorated pathological injury. Lung H&E staining shows evident histopathological changes, including alveolar wall congestion and thickening (red arrows) and inflammatory cell infiltration (black arrows) in the control group, which were milder in the ARF1-KD group. Data are representative of similar results from testing five animal samples per group. Scale bars, 100 μm. Source data are provided as a Source data file.
