Fig. 1 |. A haploid genetic screen identifies PCDH1 as a host factor for ANDV and SNV entry and infection.

a, b, Relative infectivity of rVSVs bearing the indicated viral glycoproteins. Wild-type (WT) and PCDH1-knockout (KO) HAP1 cell lines lacking (-cDNA) or expressing (+cDNA) WT human PCDH1 cDNA were exposed to rVSVs expressing hantavirus glycoproteins (rVSV-GPs) (a) or to hantaviruses (HVs) (b).a, Infected cells positive for enhanced green fluorescent protein (eGFP; pseudocoloured green) were detected by fluorescence microscopy. Representative images are shown. Scale bar, 100 μm. b, Hantavirus-infected cells were detected and enumerated by immunofluorescence microscopy. Averages ± s.d. from three experiments are shown in b; n = 6 (ANDV); n = 5 (SNV); WT versus PCDH1-KO cells, two-way ANOVA with Tukey’s test, ***P< 0.001 (n indicates the number of biologically independent samples). c, Expression of PCDH1 in HUVECs and HPMECs was detected by immunostaining with PCDHl-specific monoclonal antibody (mAb) 3305 or negative control antibody (see Extended Data Fig. 4d) and visualized by immunofluorescence microscopy. Scale bar, 20 μm. Experiments were performed three times with similar results. d, HPMECs transduced to co-express the endonuclease Cas9 and control or single-guide RNAs (sgRNAs) targeting PCDH1 were exposed to rVSVs. The results are averages ± s.d. from five experiments; n = 16 for ANDV; n = 18 for SNV; n = 14 for HTNV. PCDH1 sgRNA versus control sgRNA, two-way ANOVA with Sidak’s test; NS, P > 0.05; ****P < 0.0001.