Differentiation-dependent changes in levels of C/EBPβ repressors and activators regulate human papillomavirus type 31 late gene expression

The liver-enriched transcriptional activator protein (LAP) isoform of CCAAT/enhancer binding proteinβ (C/EBPβ) is shown to be a major activator of differentiation-dependent human papillomavirus (HPV) late gene expression, while the liver-enriched inhibitory protein (LIP) isoform negatively regulates late expression. In undifferentiated cells, LIPs act as dominant-negative repressors of late expression, and upon differentiation, LIP levels are significantly reduced, allowing LAP-mediated activation of the late promoter. Importantly, knockdown of C/EBPβ isoforms blocks activation of late gene expression from complete viral genomes upon differentiation.