Host genetic heterogeneity drives differential infection patterns of HCoV-OC43 in human respiratory organoids

Infection of donor-derived HAE-ALI models with HCoV-OC43 1018 induced striking donor-specific transcriptional responses. Principal Component Analysis (PCA) of transcriptome data revealed a clear separation between infected and mock-infected groups along the first principal component (PC1), which accounted for the majority of the variance in gene expression profiles. Triplicate biological samples for each experimental condition clustered tightly, indicating the high reproducibility of the viral infection and RNA-seq data. A hierarchical clustering heatmap of the significantly differentially expressed genes (DEGs) further supported the PCA results, displaying distinct expression patterns that clearly discriminated between the NC13-infected, NC14-infected, and control groups. Volcano plot analysis identified DEGs with statistical significance and substantial fold change, revealing a large number of DEGs in the infected versus control groups for both NC13 and NC14 donor-derived cultures.