Human papillomavirus type 16 late gene expression is regulated by cellular RNA processing factors in response to epithelial differentiation

Abstract

HPV16 (human papillomavirus type 16) is a 7.9 kb double-stranded DNA virus that infects anogenital mucosal epithelia. In some rare cases, in women, infection can progress to cervical cancer. HPV16 gene expression is regulated through use of multiple promoters and alternative splicing and polyadenylation. The virus genome can be divided into an early and a late coding region. The late coding region contains the L1 and L2 genes. These encode the virus capsid proteins L1 and L2; protein expression is confined to the upper epithelial layers and is regulated post-transcriptionally in response to epithelial differentiation. A 79 nt RNA regulatory element, the LRE (late regulatory element), involved in this regulation is sited at the 3′-end of the L1 gene and extends into the late 3′-UTR (3′-untranslated region). This element represses late gene expression in differentiated epithelial cells and may activate it in differentiated cells. The present paper describes our current knowledge of LRE RNA–protein interaction and their possible functions.