Biology of human papillomaviruses

Abstract

Human papillomaviruses (HPVs) cause squamous cancers of epithelial surfaces, of which genital cancers are the most common. In this article we have attempted to describe the properties and functions of the viral proteins of HPV type 16, a common cause of genital cancers, and have tried to suggest how their expression may lead to a dysregulated cell which may become malignant. These viruses are attempting to replicate in terminally differentiating keratinocytes and must stimulate G1 to S-phase progression for the replication of their genome. As part of the successful completion of replication and assembly of infectious virus particles, the virus needs at least partial differentiation to occur. Therefore, at the same time as differentiation is occurring, the nuclei of infected cells are in S-phase. While the mechanisms of action of the viral proteins are not completely understood, researchers are making progress and this article strives to bring together the conclusions from some of this work.

Figure 1

Schematic of the HPV-16 genome organization. The early genes are solid grey and the late genes are marble grey. The base pairs of the open reading frames are shown and the ATG start codon is shown in italics. E4 is spliced to the N-terminal of E1 (E1^E4) since it has no ATG of its own. The poly A + signals for the early and late mRNA are shown (pA). The origin (ori) of replication and the upstream regulatory region (URR) or the main early promoter region are indicated.