Fig. 5: SARS-CoV-2 infection promotes GP73 production and secretion.
From: GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia
a,b, Supernatant GP73 levels in Huh-7 cells infected with SARS-CoV-2 at the indicated multiplicity of infection (MOI) for 24 h (a) or with SARS-CoV-2 (MOI 0.1) for the indicated times (b). P = 0.0177 for 0.01 MOI versus 0 MOI, P = 0.0002 for 0.1 MOI versus 0 MOI (a), P = 0.0049 for 0.1 MOI versus 0 MOI (24 h), P < 0.0001 for 0.1 MOI versus 0 MOI (48 h), P = 0.0010 for 0.1 MOI versus 0 MOI (72 h) by two-way ANOVA followed by Bonferroni’s post hoc test. c, Intracellular GP73 levels in Huh-7 cells infected with SARS-CoV-2 (CoV-2) at the indicated MOIs for 24 h. d, Representative of three confocal immunofluorescence images of GP73 staining in liver and lung sections from three MASCp6-infected mice. Green represents GP73 and blue represents the nucleus. e, GP73 mRNA expression in lung, liver and kidney tissues from mice inoculated with 1.6 × 104 plaque-forming units (p.f.u.) of MASCp6 and killed at day 2 after inoculation (n = 6). P = 0.0079 for infected versus mock (lung), P = 0.0389 for infected versus mock (liver) by two-tailed Student’s t-tests. f,g, Supernatant GP73 levels in Huh-7 cells transfected with plasmids expressing the indicated SARS-CoV-2 proteins (f) or different concentrations of Flag-N (g). P = 0.0097 for NSP12 versus vector, P = 0.0044 for NSP14 versus vector, P = 0.0012 for S versus vector and P = 0.0031 for N versus vector by two-tailed Student’s t-tests (f), P = 0.0036 for 0.5 μg versus 0 μg and P < 0.0001 for 4 μg versus 0 μg by one-way ANOVA followed by Bonferroni’s post hoc test (g). h, Supernatant GP73 levels in Huh-7 cells challenged with SARS-CoV-2pp or VSV-Gpp for the indicated times. P = 0.0205 for SARS-2-Spp versus VSV-Gpp (12 h), P = 0.0004 for SARS-2-Spp versus VSV-Gpp (24 h) and P = 0.0006 for SARS-2-Spp versus VSV-Gpp (48 h) by two-way ANOVA followed by Bonferroni’s post hoc test. i,j, Immunoprecipitation analysis of GP73 interaction with N (i) or S (j) protein in 293T cells transfected with Flag-N or Flag-S. Animal and cell-based studies were performed independently at least three biological replicates with comparable results. Data are mean ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001.
