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  • The EMBO Journal (2005) 24, 1821 - 1830
  • doi:10.1038/sj.emboj.7600651

Published online: 28 April 2005

HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs

Michelle S Longworth1, Regina Wilson1 and Laimonis A Laimins1

  1. Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence to:

Laimonis A Laimins, Department of Microbiology and Immunology, Northwestern University, Morton 6-693, 303 E Chicago Ave, Chicago, IL 60611, USA. Tel.: +1 312 503 0648; Fax: +1 312 503 0649; E-mail: l-laimins@northwestern.edu

Received 6 December 2004; Accepted 24 March 2005

The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by associating with Rb family members as well class I histone deacetylases (HDACs). The binding of HDACs is also important for the maintenance of viral episomes during the differentiation-dependent productive life cycle. The effects of E7 and other viral proteins on E2F family members were examined in differentiating keratinocytes. E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs. Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7 directly modulates viral replication and identifies E2F2 as a possible target for antiviral therapies.

  • Keywords:

    • E2F2,
    • E7,
    • histone deacetylase,
    • human papillomavirus