title: Adenovirus E4orf4 induces HPV-16 late L1 mRNA production.
abstract: The adenovirus E4orf4 protein regulates the switch from early to late gene expression during the adenoviral replication cycle. Here we report that overexpression of adenovirus E4orf4 induces human papillomavirus type 16 (HPV-16) late gene expression from subgenomic expression plasmids. E4orf4 specifically overcomes the negative effects of two splicing silencers at the two late HPV-16 splice sites SD3632 and SA5639. This results in the production of HPV-16 spliced L1 mRNAs. We show that the interaction of E4orf4 with protein phosphatase 2A (PP2A) is necessary for induction of HPV-16 late gene expression. Also an E4orf4 mutant that fails to bind the cellular splicing factor ASF/SF2 fails to induce L1 mRNA production. Collectively, these results suggest that dephosphorylation of SR proteins by E4orf4 activates HPV-16 late gene expression. Indeed, a mutant ASF/SF2 protein in which the RS-domain had been deleted could itself induce HPV-16 late gene expression, whereas wild type ASF/SF2 could not.
authors.affiliation: Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Somberg
authors.forename: Margaret
authors.initials: M
authors.lastname: Rush
authors.forename: Joanna
authors.initials: J
authors.lastname: Fay
authors.forename: Fergus
authors.initials: F
authors.lastname: Ryan
authors.forename: Helen
authors.initials: H
authors.lastname: Lambkin
authors.forename: Göran
authors.initials: G
authors.lastname: Akusjärvi
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
mesh_terms: D036022:Capsid Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis*; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; C121517:E4orf4 protein, adenovirus; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D000068103:Serine-Arginine Splicing Factors; C063317:L1 protein, Human papillomavirus type 16; D054648:Protein Phosphatase 2