Fig. 3.

APOE4 features attenuated inhibitory effect on cellular entry of SARS-CoV-2 pseudo-virus, Spike/ACE2 interaction and binding of Spike to the cell surface compared to APOE3. a–d Confocal imaging (a, b) and flow cytometry (c, d) analyses of VSV-ΔG-SARS-CoV-2-EGFP pseudo-viral load in 293T-ACE2 cells in the absence (Vehicle) or the presence of recombinant APOE3 or APOE4 proteins. n = 4 independent experiments. e–h Assessment of SARS-CoV-2 pseudo-viral load in APOE3-TR or APOE4-TR mouse lung expressing human ACE2. e Flow chart of study design. f qRT-PCR analysis of pseudo-viral EGFP mRNA levels in APOE3-TR or APOE4-TR mouse lung tissues transduced with AAV-ACE2. n = 3 mice per group. g, h Confocal imaging analysis of VSV-ΔG-SARS-CoV-2-EGFP pseudo-viral load in lung tissues. n = 4 mice per group. i–j Protein pull-down analysis of Spike-His/ACE2-Fc interactions in the presence of recombinant APOE3 or APOE4 proteins. k–n Super-resolution (k, l) and immuno-electron (m, n) microscopic analyses of surface-bound Spike-Fc proteins in 293T-ACE2 cells in the presence of recombinant APOE3 or APOE4 proteins. n = 4 independent experiments. Data are presented as mean ± S.E.M. Statistical significances were assessed by unpaired, two-sided Mann–Whitney U-tests. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001