HPV-18 E2circumflexE4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation

Journal Article · Fri Jul 20 00:00:00 EDT 2012 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2012.03.023· OSTI ID:22149283

Tan, Chye Ling ^[1]; Gunaratne, Jayantha ^[2]; Lai, Deborah ^[1]; Carthagena, Laetitia ^[3]; Wang, Qian ^[4]; Xue, Yue Zhen; Quek, Ling Shih ^[1]; Doorbar, John ^[4]; Bachelerie, Francoise ^[3]; Thierry, Francoise ^[1]; Bellanger, Sophie ^[1]

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1. Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore)
2. Mass Spectrometry and Systems Biology Laboratory, Institute of Molecular and Cell Biology, A-STAR, Biopolis, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore)
3. UMR-S996, Universite Paris-Sud 11, 32 rue des Carnets, 92140 Clamart (France)
4. MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London N10 3UE (United Kingdom)

The Human Papillomavirus (HPV) E4 is known to be synthesized as an E1circumflexE4 fusion resulting from splice donor and acceptor sites conserved across HPV types. Here we demonstrate the existence of 2 HPV-18 E2circumflexE4 transcripts resulting from 2 splice donor sites in the 5 Prime part of E2, while the splice acceptor site is the one used for E1circumflexE4. Both E2circumflexE4 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, E2circumflexE4-S and E2circumflexE4-L. Whereas we could not differentiate E2circumflexE4-S from E1circumflexE4 in vivo, E2circumflexE4-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 E2circumflexE4 products.

• OSTI ID: 22149283
• Journal Information: Virology, Vol. 429, Issue 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOPSY
CHIMERAS
IN VITRO
IN VIVO
PATIENTS
PROTEINS
RNA
SPLICING
TRANSCRIPTION