Extended Data Fig. 7: Characterizing MPXV infection in the liver of a patient and in organoids based models. | Nature Biomedical Engineering

Extended Data Fig. 7: Characterizing MPXV infection in the liver of a patient and in organoids based models.

From: Macrophage-augmented organoids recapitulate the complex pathophysiology of viral diseases and enable development of multitarget therapeutics

Extended Data Fig. 7

a, Image of the liver from a patient died from disseminated mpox. Here we specifically focused on liver involvement in one case who developed MPXV-hepatitis. In the liver, we observed steatosis, diffuse congestion, focal subcapsular hemorrhages and scattered lobular nodules. b, Histology (H&E) of the liver section from a patient without MPXV infection (as a negative control). c, Immunohistochemical staining against the MPXV antigens showed negative signal in this negative control liver tissue, indicating the specificity of the antibody. d, Biliary duct exhibiting cholangiocytes with pykontic nuclei and hypereosinophiliccytoplasm (H&E). e, Focal MPXV-hepatitis (arrow), and the adjacent hepatocytes showing reduced expression of E-cadherin by immunohistochemical staining. f, Immunohistochemical staining of bacterial lipopolysaccharide (LPS) detected bacterial fragments in the cytoplasm of Kupffer cells (black arrows) or entire bacilli in the sinusoids (red arrows). g, Confocal imaging of MPXV infection in ICOs complementary to Fig. 7e. EpCAM (yellow): epithelial marker; dsRNA (red): MPXV double-stranded RNA; DAPI (blue): nuclear staining. h, Quantification of MPXV genomic DNA in the supernatant harvested from infected adult ICOs (O), hepatic differentiated ICOs (HepO), and fetal ICOs (FetalO) 4 days post-inoculation (n = 4, biological replicates), complementary to Fig. 7j. i, Confocal imaging shows MPXV infection in macrophages of MaugOs constructed from hepatic differentiated organoids, complementary to Fig. 8b. CD68 (red): macrophage marker; MPXV (green): staining against the virions; DAPI (blue): nuclear staining. j, Confocal imaging of uninfected macrophages (M) and ICOs infected with MPXV for 2days, and then integrated with macrophages for 24 hours (MPXV MaugO). CK7 (red): marker of biliary epithelium; MPXV (green): staining against the virions; DAPI (blue): nuclear staining. k, Quantification of MPXV viral RNA in MaugOs constructed by different approaches (n = 4, biological replicates). ICOs were infected with MPXV for 2 or 5 days, and then integrated with macrophages for 24 or 48 hours. Relating to Fig. 8h, ICOs were infected with MPXV for 5 days, and then integrated with macrophages for 24 or 48 hours.; Two tailed Mann-Whitney U test. Exact p values are labelled. l, The expression of inflammatory genes in ICOs infected with MPXV for 2 days, and then integrated with macrophages for 24 hours (n = 4). (h, k, i) Data are mean ± SD. *p < 0.05; **p < 0.01.

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