The homeobox transcription factor HOXC13 upregulates human papillomavirus E1 gene expression and contributes to viral genome maintenance

Abstract

Human papillomavirus (HPV) infects the basal cells of epithelia and maintains its genome stably as episomes. However, the mechanisms of viral genome maintenance are not fully understood. Here, using normal human immortalized keratinocytes (NIKS), we identified the homeobox transcription factor HOXC13 as a critical host factor for retaining the copy number of HPV genomes in the cell. HOXC13 knockdown in NIKS significantly decreased mRNA levels of the E1 gene, which encodes a DNA helicase required for HPV genome replication, accompanied by a reduction of the viral genome copy number. Chromatin immunoprecipitation assays revealed HOXC13 binding to the long control region that regulates E1 expression. These results indicate that HOXC13 plays invaluable roles in maintaining HPV persistent infection through E1 gene upregulation.