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 protein beta (C/EBP beta) 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/EBP beta isoforms blocks activation of late gene expression from complete viral genomes upon differentiation.