HPV-18 E2^E4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation

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• 作者：Chye Ling Tan^a ; Jayantha Gunaratne^b ; Deborah Lai^a ; Laetitia Carthagena^c ; Qian Wang^d ; Yue Zhen Xue^a ; Ling Shih Quek^a ; John Doorbar^d ; Franç ; oise Bachelerie^c ; Franç ; oise Thierry^a ; ^{francoise.thierry@imb.a-star.edu.sg} ; Sophie Bellanger^a ; ^{sophie.bellanger@imb.a-star.edu.sg}
• 关键词：HPV ; E2^E4 ; Splicing ; E4 ; E2 ; Transcription ; RNA ; Differentiation ; Papillomavirus
• 刊名：Virology
• 出版年：2012
• 出版时间：20 July, 2012
• 年：2012
• 卷：429
• 期：1
• 页码：47-56
• 全文大小：1214 K

文摘

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.