Fig. 4: Productive infection and cellular tropism of SARS-CoV-2 in human intestinal organoids.

a, Culture media were collected from the infected human enteroids and subjected to viral load detection and viral titration. Data present the mean and s.d. of one representative experiment, n = 3 replicates. Independent experiments were performed more than three times. Two-tailed Student’s t-test. b, Culture media collected from the inoculated colonoids were subjected to viral load detection. Data present the mean and s.d. of one representative experiment, n = 3 replicates. Independent experiments were performed two times. c, The human enteroids were fixed after a low MOI (left) or high MOI (right) inoculation and subjected to immunostaining to identify the viral NP (green)-positive cells. Nuclei and actin filaments were counterstained with DAPI (blue) and Phalloidin-647 (purple), respectively. Scale bar, 10 µm. Independent experiments were performed more than three times. d, After a high MOI inoculation, the human enteroids were co-labeled with α-NP (green) and α-Villin (red). Arrows show NP-positive cells coexpressing Villin. Scale bar, 10 µm. e, Induction of IFNL2 and IFNL3 in the human enteroids at 48 hpi. Results show fold change of GAPDH-normalized expression level in the infected enteroids relative to that in the mock-infected enteroids. Data represent mean and s.d. of one representative experiment, n = 3 replicates. Independent experiments were performed three times. Two-tailed Student’s t-test. The same RNA samples were applied to detect 84 human inflammatory cytokines and receptors. The heat map shows the differentially expressed genes in the infected enteroids (n = 3) relative to mock-infected organoids (n = 3). Genes with a fold change of more than 2 are illustrated; star (*) indicates a change of significant difference.