title: HPV-18 E2^E4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation.
abstract: The Human Papillomavirus (HPV) E4 is known to be synthesized as an E1^E4 fusion resulting from splice donor and acceptor sites conserved across HPV types. Here we demonstrate the existence of 2 HPV-18 E2^E4 transcripts resulting from 2 splice donor sites in the 5' part of E2, while the splice acceptor site is the one used for E1^E4. Both E2^E4 transcripts are up-regulated by keratinocyte differentiation in vitro and can be detected in clinical samples containing low-grade HPV-18-positive cells from Pap smears. They give rise to two fusion proteins in vitro, E2^E4-S and E2^E4-L. Whereas we could not differentiate E2^E4-S from E1^E4 in vivo, E2^E4-L could be formally identified as a 23 kDa protein in raft cultures in which the corresponding transcript was also found, and in a biopsy from a patient with cervical intraepithelial neoplasia stage I-II (CINI-II) associated with HPV-18, demonstrating the physiological relevance of E2^E4 products.
authors.affiliation: Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore.
authors.forename: Chye Ling
authors.initials: CL
authors.lastname: Tan
authors.forename: Jayantha
authors.initials: J
authors.lastname: Gunaratne
authors.forename: Deborah
authors.initials: D
authors.lastname: Lai
authors.forename: Laetitia
authors.initials: L
authors.lastname: Carthagena
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yue Zhen
authors.initials: YZ
authors.lastname: Xue
authors.forename: Ling Shih
authors.initials: LS
authors.lastname: Quek
authors.forename: John
authors.initials: J
authors.lastname: Doorbar
authors.forename: Françoise
authors.initials: F
authors.lastname: Bachelerie
authors.forename: Françoise
authors.initials: F
authors.lastname: Thierry
authors.forename: Sophie
authors.initials: S
authors.lastname: Bellanger
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D005260:Female; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000821:virology; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000503:physiopathology / Q000821:virology*; D022821:RNA Splice Sites; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism
chemical_list: D009856:Oncogene Proteins, Viral; D022821:RNA Splice Sites; D012367:RNA, Viral; C069102:oncogene protein E2, Human papillomavirus type 18; C468296:oncogene protein E4, Human papillomavirus type 18