title: HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting early polyadenylation.
abstract: 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.
authors.affiliation: Section of Medical Microbiology, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.forename: Monika
authors.initials: M
authors.lastname: Somberg
authors.forename: Xiaoze
authors.initials: X
authors.lastname: Li
authors.forename: Ellenor
authors.initials: E
authors.lastname: Backström Winquist
authors.forename: Joanna
authors.initials: J
authors.lastname: Fay
authors.forename: Fergus
authors.initials: F
authors.lastname: Ryan
authors.forename: David
authors.initials: D
authors.lastname: Pim
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
mesh_terms: D036022:Capsid Proteins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D026723:Polyadenylation / Q000502:physiology*; D039104:RNA 3' Polyadenylation Signals / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; D012097:Repressor Proteins; C062495:oncogene protein E7, Human papillomavirus type 6; C063317:L1 protein, Human papillomavirus type 16