This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Collier, B. Articles by Schwartz, S. Search for Related Content PubMed PubMed Citation Articles by Collier, B. Articles by Schwartz, S.

Specific Inactivation of Inhibitory Sequences in the 5' End of the Human Papillomavirus Type 16 L1 Open Reading Frame Results in Production of High Levels of L1 Protein in Human Epithelial Cells

Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden

Received 23 August 2001/ Accepted 14 December 2001

The expression of human papillomavirus type 16 late genes encoding virus capsid proteins L1 and L2 is restricted to terminally differentiated epithelial cells in the superficial layers of the squamous epithelium. We wish to understand the molecular mechanisms that determine the levels of expression of the human papillomavirus type 16 late genes. We have previously shown that the L1 coding region contains inhibitory sequences. Here we extend previous findings to show that the 5' end of the L1 gene contains strong inhibitory sequences but that the 3' end does not. We show that the first 514 nucleotides of the L1 coding region contain multiple inhibitory elements that act independently of one another and that the major inhibitory element is located within the first 129 nucleotides of the L1 gene. Introduction of point mutations in the inhibitory elements in the 5' end of the L1 gene which altered the RNA sequence without affecting the protein sequence specifically inactivated the inhibitory elements and resulted in production of high levels of human papillomavirus type 16 L1 mRNA and protein in human epithelial cells. Furthermore, we show that inhibitory sequences are present in the L1 coding regions of multiple human papillomavirus types, demonstrating that these elements are conserved among the human papillomaviruses, and suggest that they have an important function in the viral life cycle.

This article has been cited by other articles:

• Somberg, M., Zhao, X., Frohlich, M., Evander, M., Schwartz, S. (2008). Polypyrimidine Tract Binding Protein Induces Human Papillomavirus Type 16 Late Gene Expression by Interfering with Splicing Inhibitory Elements at the Major Late 5' Splice Site, SD3632. J. Virol. 82: 3665-3678 [Abstract] [Full Text]  
• Gu, W., Ding, J., Wang, X., de Kluyver, R. L., Saunders, N. A., Frazer, I. H., Zhao, K.-N. (2007). Generalized substitution of isoencoding codons shortens the duration of papillomavirus L1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation. Nucleic Acids Res 0: gkm496v1-13 [Abstract] [Full Text]  
• Maclean, J., Koekemoer, M., Olivier, A. J., Stewart, D., Hitzeroth, I. I., Rademacher, T., Fischer, R., Williamson, A.-L., Rybicki, E. P. (2007). Optimization of human papillomavirus type 16 (HPV-16) L1 expression in plants: comparison of the suitability of different HPV-16 L1 gene variants and different cell-compartment localization. J. Gen. Virol. 88: 1460-1469 [Abstract] [Full Text]  
• Zhao, K.-N., Gu, W., Fang, N. X., Saunders, N. A., Frazer, I. H. (2005). Gene Codon Composition Determines Differentiation-Dependent Expression of a Viral Capsid Gene in Keratinocytes In Vitro and In Vivo. Mol. Cell. Biol. 25: 8643-8655 [Abstract] [Full Text]  
• Rush, M., Zhao, X., Schwartz, S. (2005). A Splicing Enhancer in the E4 Coding Region of Human Papillomavirus Type 16 Is Required for Early mRNA Splicing and Polyadenylation as Well as Inhibition of Premature Late Gene Expression. J. Virol. 79: 12002-12015 [Abstract] [Full Text]  
• Oberg, D., Fay, J., Lambkin, H., Schwartz, S. (2005). A Downstream Polyadenylation Element in Human Papillomavirus Type 16 L2 Encodes Multiple GGG Motifs and Interacts with hnRNP H. J. Virol. 79: 9254-9269 [Abstract] [Full Text]  
• Zhao, X., Oberg, D., Rush, M., Fay, J., Lambkin, H., Schwartz, S. (2005). A 57-Nucleotide Upstream Early Polyadenylation Element in Human Papillomavirus Type 16 Interacts with hFip1, CstF-64, hnRNP C1/C2, and Polypyrimidine Tract Binding Protein. J. Virol. 79: 4270-4288 [Abstract] [Full Text]  
• Berg, M., DiFatta, J., Hoiczyk, E., Schlegel, R., Ketner, G. (2005). Viable adenovirus vaccine prototypes: High-level production of a papillomavirus capsid antigen from the major late transcriptional unit. Proc. Natl. Acad. Sci. USA 102: 4590-4595 [Abstract] [Full Text]  
• Zhao, X., Rush, M., Schwartz, S. (2004). Identification of an hnRNP A1-Dependent Splicing Silencer in the Human Papillomavirus Type 16 L1 Coding Region That Prevents Premature Expression of the Late L1 Gene. J. Virol. 78: 10888-10905 [Abstract] [Full Text]  
• Gu, W., Li, M., Zhao, W. M., Fang, N. X., Bu, S., Frazer, I. H., Zhao, K.-N. (2004). tRNASer(CGA) differentially regulates expression of wild-type and codon-modified papillomavirus L1 genes. Nucleic Acids Res 32: 4448-4461 [Abstract] [Full Text]  
• Oberg, D., Collier, B., Zhao, X., Schwartz, S. (2003). Mutational Inactivation of Two Distinct Negative RNA Elements in the Human Papillomavirus Type 16 L2 Coding Region Induces Production of High Levels of L2 in Human Cells. J. Virol. 77: 11674-11684 [Abstract] [Full Text]