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HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting early polyadenylation.

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Author

  • Cecilia Johansson
  • Monika Somberg
  • Xiaoze Li
  • Ellenor Winquist
  • Joanna Fay
  • Fergus Ryan
  • David Pim
  • Lawrence Banks
  • Stefan Schwartz

Summary, in English

We provide evidence that the human papillomavirus (HPV) E2 protein regulates HPV late gene expression. High levels of E2 caused a read-through at the early polyadenylation signal pAE into the late region of the HPV genome, thereby inducing expression of L1 and L2 mRNAs. This is a conserved property of E2 of both mucosal and cutaneous HPV types. Induction could be reversed by high levels of HPV-16 E1 protein, or by the polyadenylation factor CPSF30. HPV-16 E2 inhibited polyadenylation in vitro by preventing the assembly of the CPSF complex. Both the N-terminal and hinge domains of E2 were required for induction of HPV late gene expression in transfected cells as well as for inhibition of polyadenylation in vitro. Finally, overexpression of HPV-16 E2 induced late gene expression from a full-length genomic clone of HPV-16. We speculate that the accumulation of high levels of E2 during the viral life cycle, not only turns off the expression of the pro-mitotic viral E6 and E7 genes, but also induces the expression of the late HPV genes L1 and L2.

Publishing year

2012

Language

English

Pages

3212-3227

Publication/Series

EMBO Journal

Volume

31

Issue

14

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Biochemistry and Molecular Biology

Status

Published

Research group

  • Molecular virology

ISBN/ISSN/Other

  • ISSN: 1460-2075