Fig. 6: Age-related susceptibility to HCoV-229E driven by UHRF1 epigenetic modulation.

A, B Transcriptomic analysis of UHRF1 (A) and APN (B) expression in lung tissues from three age groups. C Correlation analysis of UHRF1 and APN transcription levels with age. D UHRF1 and APN expression levels in single-cell RNA-seq (scRNA-seq) data of lung tissues from three age groups. The dot plot shows the percentage of cells in each population with detectable gene expression. Dot size indicates the percentage of positive cells, and color indicates mean expression levels. E Analysis of UHRF1 and APN gene expression in scRNA-seq data of various lung cell types. Dot size indicates the percentage of positive cells, and color indicates the mean expression levels. F, G Expression levels of UHRF1 (F) and APN (G) in alveolar macrophages from young (n = 4) and old (n = 8) donors. Relative mRNA levels were determined by qRT-PCR, and expressed relative to young donors. H–J HCoV-229E infection in alveolar macrophages from young and old donors. At 24 h post-infection, viral RNA in cells was determined by qRT-PCR (H); At 12 or 24 h post-infection, virus production in the supernatant was titrated by focus-forming assay (I). Cytokine expression in cells was determined by qRT-PCR (J); K, L Bisulfite sequencing of CpG sites in APN proximal promoter from one representative (K) or pooled (L) young and old donors. Methylation (Meth) rates were calculated as the ratio of methylated sites to the total number of sites tested. M Schematic of the role of UHRF1 in coronavirus infection. UHRF1 restricts coronavirus infection through epigenetic silencing of host factors, particularly the entry receptor APN for HCoV-229E. Created in BioRender. Wang, P. (2025) https://BioRender.com/ebsq4he. Error bars represent standard deviations (F–H, L), mean ± s.d.; the median values are shown (I, J). One-way ANOVA with Dunnett’s test (A, B); unpaired, two-sided t-test (F–H, L); Two-way ANOVA with Sidak’s test (I); Mann-Whitney test (J). Young (F–J, L), n = 8; Old (F–J, L), n = 4. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns, not significant.