Cis-Acting Negative RNA Elements on Papillomavirus Late mRNAs

Papillomaviruses comprise a large number of related small DNA tumor viruses with tropism for squamous epithelial cells. The papillomavirus replication cycle is strictly linked to the differentiation stages of the infected epithelial cells, and the expression of L1 and L2 capsid proteins from the viral late genes is primarily detected in the superficial layers of terminally differentiated cells. Expression of the L1 and L2 genes is blocked in nonterminally differentiated cells and the production of progeny virus is delayed until the infected cell reaches the upper strata of the squamous epithelium. This property presumably aids the papillomavirus to evade the immune surveillance of the host and allows establishment of persistent infections. Late gene expression levels are determined in part by regulatory RNA sequences on the papillomavirus mRNAs. This review focuses primarily on negativecis-acting elements on late papillomavirus mRNAs and their candidatetrans-acting factors. Identification and characterization of these components will contribute to our understanding of the regulated expression of papillomaviruses in mammalian cells.