Virology, Nebraska Center for


Date of this Version



Virology. 2010 September 30; 405(2): 342–351.


© 2010 Elsevier Inc. All rights reserved.


Anogenital cancers and head and neck cancers are causally-associated with infection by high-risk

human papillomavirus (HPV). The mechanism by which high-risk HPVs contribute to

oncogenesis is poorly understood. HPV16 encodes three genes (HPV16 E5, E6, and E7) that can

transform cells when expressed independently. HPV16 E6 and E7 have well-described roles

causing genomic instability and unregulated cell cycle progression. The role of HPV16 E5 in cell

transformation remains to be elucidated. Expression of HPV16 E5 results in enlarged, polyploid

nuclei that are dependent on the level and duration of HPV16 E5 expression. Live-cell imaging

data indicate these changes do not arise from cell-cell fusion or failed cytokinesis. The increase in

nuclear size is a continual process that requires DNA synthesis. We conclude HPV16 E5 produces

polyploid cells by endoreplication. These findings provide insight into how HPV16 E5 can

contribute to cell transformation.