The regulation of cell proliferation by the papillomavirus early proteins

The human papillomavirus (HPV) E6 and E7 oncogenes have direct effects on host cell proliferation. The viral E2 protein regulates transcription of E6 and E7 and thereby has an indirect effect on cell proliferation. In HPV-induced tumours, misappropriate random integration of the viral genome into the host chromosome often leads to disruption of the E2 gene and the loss of E2 expression. This results in cessation of the virus life cycle and the deregulation of E6 and E7 and is an important step in tumourigenesis. However, prior to these integration events, E2 can interact directly with the E6 and E7 proteins and modulate their activities. E2 also interacts with a variety of host proteins, including the p53 tumour suppressor protein. Here we outline evidence that suggests a role for E2 in the regulation of cell proliferation, and we discuss the importance of this regulation in viral infection and cervical tumourigenesis.