Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

Lulin Hu, Kendra Plafker, Valeriya Vorozhko, Rosemary E. Zuna, Marie H. Hanigan, Gary J. Gorbsky, Scott M. Plafker, Peter C Angeletti, Brian P. Ceresa

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalVirology
Volume384
Issue number1
DOIs
StatePublished - Feb 5 2009

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Human papillomavirus 16
Cell Fusion
Oncogenes
Video Microscopy
DNA Viruses
Keratinocytes
Carcinogenesis
Cell Proliferation
Neoplasms
Proteins

Keywords

  • Cell fusion
  • Cervical cancer
  • HPV

ASJC Scopus subject areas

  • Virology

Cite this

Hu, L., Plafker, K., Vorozhko, V., Zuna, R. E., Hanigan, M. H., Gorbsky, G. J., ... Ceresa, B. P. (2009). Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion. Virology, 384(1), 125-134. https://doi.org/10.1016/j.virol.2008.10.011

Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion. / Hu, Lulin; Plafker, Kendra; Vorozhko, Valeriya; Zuna, Rosemary E.; Hanigan, Marie H.; Gorbsky, Gary J.; Plafker, Scott M.; Angeletti, Peter C; Ceresa, Brian P.

In: Virology, Vol. 384, No. 1, 05.02.2009, p. 125-134.

Research output: Contribution to journalArticle

Hu, L, Plafker, K, Vorozhko, V, Zuna, RE, Hanigan, MH, Gorbsky, GJ, Plafker, SM, Angeletti, PC & Ceresa, BP 2009, 'Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion', Virology, vol. 384, no. 1, pp. 125-134. https://doi.org/10.1016/j.virol.2008.10.011
Hu L, Plafker K, Vorozhko V, Zuna RE, Hanigan MH, Gorbsky GJ et al. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion. Virology. 2009 Feb 5;384(1):125-134. https://doi.org/10.1016/j.virol.2008.10.011
Hu, Lulin ; Plafker, Kendra ; Vorozhko, Valeriya ; Zuna, Rosemary E. ; Hanigan, Marie H. ; Gorbsky, Gary J. ; Plafker, Scott M. ; Angeletti, Peter C ; Ceresa, Brian P. / Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion. In: Virology. 2009 ; Vol. 384, No. 1. pp. 125-134.
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