The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon-alpha.
It is now well recognized that cervical cancer is caused by infection with certain human papillomavirus (HPV) subtypes and while interferon-alpha (IFN-alpha) is used to treat HPV-infected lesions, HPV appears to have developed a means to avoid the effects of IFN-alpha. Clinically, resistance appears to be associated with the expression of the E7 oncoprotein. Here we investigated the effects of expression in cells of the E7 protein from high- and low-risk papillomavirus subtypes on a range of responses to IFN-alpha. 2fTGH, a cell line dependent on IFN-alpha for growth in selection medium, grew significantly less well in the presence of E7, and the antiproliferative effects of IFN-alpha upon epithelial cells was lost upon E7 expression. The antiviral effects of IFN-alpha were abrogated in E7-expressing cells. Loss of response to IFN-alpha was found to occur in both high- and low-risk papillomaviruses. Finally, deletion of amino acids 21-24 of HPV type 16 E7 protein partially reversed repression. We conclude that E7 inhibits the functional effects of IFN-alpha and that this property is shared by all HPV subtypes tested.
Barnard
P
P
Department of Medicine, University of Queensland, Brisbane, Queensland 4102, Australia.
Payne
E
E
McMillan
N A
NA
D000998:Antiviral Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002460:Cell Line; D017353:Gene Deletion; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D027383:Papillomaviridae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D050725:Papillomavirus E7 Proteins
D000998:Antiviral Agents; D016898:Interferon-alpha; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16