Analysis of HPV16 E2 host gene expression using TERT immortalized keratinocytes (NOKs) cell lines and RNA-sequencing

HPV must reprogram host gene expression to promote infection, and HPV proteins E6 and E7 contribute to this via targeting of cellular transcription factors including p53 and pRb respectively. The HPV16 E2 protein regulated host gene expression in U2OS cells and in this study we extend these observations into NOKs that are capable of suporting late stages of the HPV16 life cycle. We observed repression of innate immune genes by E2 that are also repressed by the intact HPV16 genome in NOKs. There was a highly significant overlap of the E2 regulated genes with those regulated by the intact HPV16 genome in the same cell type. siRNA targeting of E2 reversed repression of E2 targed genes. The ability of E2 to repress innate immune genes was confirmed in an ano-genital immortalized keratinocyte cell line, N/Tert-1. Overall design: In total, 8 samples are analyzed. Two biological replicates of NOK controls, two biological replicates of NOKs containing HPV16 full genome, and two different NOKs cell lines overexpressing the HPV16 E2 protein.