Extended Data Fig. 4: GALNT2 associated with the severity or susceptibility of SARS-CoV-2 and IAV infections.

a, GALNT2 association results in influenza A virus H7N9 genome-wide association studies (GWAS). Mx1 gene (left panel) as the control. Red plots represent the SNPs associated with virus infection. b, GALNT2 association results in influenza A virus H1N1 genome-wide association studies (GWAS). Mx1 gene (left panel) as the control. Red plots represent the SNPs associated with virus infection. P values from (a) and (b) were calculated by two-tailed Firth logistic regression test, with appropriate covariates and genomic control. c, Analysis of genetic variation at the GALNT2 gene locus between SARS-CoV-2 infected patients and control populations using data from Host Genetics Initiative (https://www.covid19hg.org/). Population frequency information for the SNP was sourced from https://www.ncbi.nlm.nih.gov/snp/rs2273970. P values were calculated by two-tailed Firth logistic regression test, with appropriate covariates and genomic control. d, Huh7 cells were transfected with plasmids encoding GALNT2 (WT or four mutants), and cells then infected with SARS-CoV-2 (MOI = 0.5) and viral infection efficiency after 24 h.p.i. by IFA. Data are means ± s.d. from n = 3 or 5 independent experiments. P values from two-tailed Student’s t-test. ((ns): no significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001). e, Huh7 cells were transfected with plasmids encoding GALNT2 (WT or V554M), and cells then infected with H1N1 PR8 (MOI = 0.01) and viral infection efficiency after 24 h.p.i. by IFA. Data are means ± s.d. from n = 3 independent experiments. P values from two-tailed Student’s t-test. ((ns): no significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001). f, GALNT2 protein expression levels in Huh7 OE-GALNT2 (GALNT2-stable cells) and Huh7 GALNT2-/- cells were detected by western blot. Western blots were representative of three independent biological repeats. g, GALNT2 protein expression levels in A549 OE-GALNT2 (GALNT2-stable cells) and A549 GALNT2-/- cells were detected by western blot. Western blots were representative of three independent biological repeats. h, STAT1 protein expression levels in Huh7 STAT1-/- and A549 STAT1-/- cells were detected by western blot. Western blots were representative of three independent biological repeats. i, Huh7 WT, GALNT2-/- and reconstitution of GALNT2 in the knockout cells by transient transfection (eGFP as the control) were infected with HCoV-OC43 at MOI 0.05. Supernatants were harvested at 24, 48 and 72 h.p.i. and viral titres were determined in HRT-18 cells by FFA. Data are means ± s.d. from n = 3 independent experiments. j, Huh7 WT, GALNT2-/- and reconstitution of GALNT2 in the knockout cells by transient transfection (eGFP as the control) were infected with HCoV-229E at MOI 0.001. Supernatants were harvested at 24, 48 and 72 h.p.i. and viral titres were determined in Huh7 cells by FFA. Data are means ± s.d. from n = 3 independent experiments. k, A549 WT (Ctrl) and A549 GALNT2-/- cells were infected with IAVs at MOI of 0.01, including H1N1 (PR8 and CA04) and H3N2 (HK68). Supernatants were harvested at indicated time points and viral titres were determined on MDCK cells by FFA. Data are means ± s.d. from n = 3 independent experiments. Data are means ± s.d. from n = 3 independent experiments. P values from two-tailed Student’s t-test. (ns): no significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001).

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