Virology Journal | |
Evolutionary variation of papillomavirus E2 protein and E2 binding sites | |
Peter C Angeletti1  Mackenzie Waltke1  Adam Rogers1  | |
[1] Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583-0900, USA | |
关键词: DNA binding Domain; E2 Protein; Human papillomavirus; persistent infection; extrachromosomal DNA; | |
Others : 1156383 DOI : 10.1186/1743-422X-8-379 |
|
received in 2011-04-26, accepted in 2011-08-01, 发布年份 2011 | |
【 摘 要 】
Background
In an effort to identify the evolutionary changes relevant to E2 function, within and between papillomavirus genera, we evaluated the E2 binding sites (E2BS)s inside the long-control-region (LCR), and throughout the genomes. We identified E2BSs in the six largest genera of papillomaviruses: Alpha, Beta, Gamma, Delta, Lambda, and Xi-papillomaviruses (128 genomes), by comparing the sequences with a model consensus we created from known functional E2BSs (HPV16, HPV18, BPV1). We analyzed the sequence conservation and nucleotide content of the 4-nucleotide spacer within E2BSs. We determined that there is a statistically significant difference in GC content of the four-nucleotide E2BS spacer, between Alpha and Delta-papillomaviruses, as compared to each of the other groups. Additionally, we performed multiple alignments of E2 protein sequences using members of each genus in order to identify evolutionary changes within the E2 protein.
Results
When a phylogenetic tree was generated from E2 amino acid sequences, it was discovered that the alpha-papillomavirus genera segregates into two distinct subgroups (α1 and α2). When these subgroups were individually analyzed, it was determined that the subgroup α1 consensus E2BS favored a spacer of AAAA, whereas subgroup α2 favored the opposite orientation of the same spacer; TTTT. This observation suggests that these conserved inverted linkers could have functional importance.
【 授权许可】
2011 Rogers et al; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150407125046109.pdf | 3088KB | download | |
Figure 4. | 140KB | Image | download |
Figure 3. | 201KB | Image | download |
Figure 2. | 157KB | Image | download |
Figure 1. | 116KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]Zheng ZM, Baker CC: Papillomavirus genome structure, expression, and post-transcriptional regulation. Front Biosci 2006, 11:2286-2302.
- [2]Day PM, Lowy DR, Schiller JT: Papillomaviruses infect cells via a clathrin-dependent pathway. Virology 2003, 307:1-11.
- [3]Bosch FX, Sanjose S, Castellsague X, Moreno V, Munoz N: Papillomavirus Research: From Natural History to Vaccines and Beyond. Edited by Saveria Campo M. Wymondham: Caisreir Academic Press; 2006:19-40.
- [4]Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S: Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003, 88:63-73.
- [5]Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348:518-527.
- [6]D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML: Case-Control Study of Human Papillomavirus and Oropharyngeal Cancer. N Engl J Med 2007, 356:1944-1956.
- [7]de Villiers E-M, Fauquet C, Broker TR, Bernard H-U, zur Hausen H: Classification of papillomaviruses. Virology 2004, 324:17-27.
- [8]Hegde RS: The papillomavirus E2 proteins: structure, function, and biology. Annu Rev Biophys Biomol Struct 2002, 31:343-360.
- [9]de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H: Classification of papillomaviruses. Virology 2004, 324:17-27.
- [10]Wentzensen N, Vinokurova S, von Knebel Doeberitz M: Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res 2004, 64:3878-3884.
- [11]McBride AA, Romanczuk H, Howley PM: The papillomavirus E2 regulatory proteins. J Biol Chem 1991, 266:18411-18414.
- [12]Sakai H, Yasugi T, Benson JD, Dowhanick JJ, Howley PM: Targeted mutagenesis of the human papillomavirus type 16 E2 transactivation domain reveals separable transcriptional activation and DNA replication functions. J Virol 1996, 70:1602-1611.
- [13]Antson AA, Burns JE, Moroz OV, Scott DJ, Sanders CM, Bronstein IB, Dodson GG, Wilson KS, Maitland NJ: Structure of the intact transactivation domain of the human papillomavirus E2 protein. Nature 2000, 403:805-809.
- [14]Thain A, Jenkins O, Clarke A, Gaston K: CpG methylation directly inhibits binding of the human papillomavirus type 16 E2 protein to specific DNA sequences. J Virol 1996, 70:7233-7235.
- [15]Ferriero DU, Delarole M, Nadra AD, De Prat Gay G: Free Energy Contributions to Direct Readout of a DNA Sequence. J Biol Chem 2005, 32480-32484.
- [16]Blakaj DM, Kattamuri C, Khrapunov S, Hegde RS, Brenowitz M: Indirect Readout of DNA Sequence by Papillomavirus E2 Proteins Depends Upon Net Cation Uptake. J Mol Biol 2006, 358:224-240.
- [17]Dell G, Wilkinson KW, Tranter R, Parish J, Leo Brady R, Gaston K: Comparison of the Structure and DNA-binding Properties of the E2 Proteins from an Oncogenic and a Non-oncogenic Human Papillomavirus. J Mol Biol 2003, 334:979-991.
- [18]Hines CS, Meghoo C, Shetty S, Biburger M, Brenowitz M, Hegde RS: DNA structure and flexibility in the sequence-specific binding of papillomavirus E2 proteins. J Mol Biol 1998, 276:809-818.
- [19]Li R, Knight J, Bream G, Stenlund A, Botchan M: Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes & Development 1989, 510-526.
- [20]Sanchez IE, Dellarole M, Gaston K, de Prat Gay G: Comprehensive comparison of the interaction of the E2 master regulator with its cognate target DNA sites in 73 human papillomavirus types by sequence statistics. Nucl Acids Res 2008, 36:756-769.
- [21]Yongli Zhang, Zhiqun Xi, Rashmi S Hegde, Zippora Shakked, Crothers aDM: Predicting indirect readout effects in protein-DNA interactions. PNAS 2004, 101:8337-8341.
- [22]M Remm RB, Jenkins JR: The E2 binding sites determine the efficiency of replication for the origin of human papillomavirus type 18. Nucleic Acids Res 1992, 20:6015-6021.
- [23]Corbach GSaS: Dose-dependent regulation of the early promoter of human papillomavirus type 18 by the viral E2 protein. J Virol 1997, 71:50-58.
- [24]Ensser A, Pfister H: Epidermodysplasia verruciformis associated human papilomaviruses present a subgenus-specific organization of the regulatory genome region. Nucl Acids Res 1990, 18:3919-3922.
- [25]Piirsoo M, Ustav E, Mandel T, Stenlund A, Ustav M: Cis and trans requirements for stable episomal maintenance of the BPV-1 replicator. Embo J 1996, 15:1-11.
- [26]Stubenrauch F, Lim HB, Laimins LA: Differential requirements for conserved E2 binding sites in the life cycle of oncogenic human papillomavirus type 31. J Virol 1998, 72:1071-1077.
- [27]Sverdrup F, Khan SA: Two E2 binding sites alone are sufficient to function as the minimal origin of replication of human papillomavirus type 18 DNA. J Virol 1995, 69:1319-1323.
- [28]Li R, Knight J, Bream G, Stenlund A, Botchan M: Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes & Development 1989, 3:510-526.
- [29]Bailey TL, Elkan C: Fitting a mixture model by expectation maximization to discover motifs in biopolymers. In Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology. Menlo Park, California: AAAI Press; 1994:28-36.
- [30]Chapter 17, The Reference Sequence (RefSeq) Project In The NCBI handbook. Bethesda: National Library of Medicine (US), National Center for Biotechnology Information; 2002.
- [31]Olson M HL, Cantor C, Botstein D: A common language for physical mapping of the human genome. Science 1989, 245:1434-1435.
- [32]Pruitt KDT, T Maglott DR: NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 2007, 35(Database):D61-35.
- [33]Bailey TL, Gribskov M: Combining evidence using p-values: application to sequence homology searches. Bioinformatics 1998, 14:48-54.
- [34]Edgar RC: MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004, 32:1792-1797.
- [35]Papadopoulos JS, Agarwala R: COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics 2007, 23:1073-1079.
- [36]Narechania A, Terai M, Burk RD: Overlapping reading frames in closely related human papillomaviruses result in modular rates of selection within E2. J Gen Virol 2005, 86:1307-1313.
- [37]Strauss JK, Maher LJ: DNA bending by asymmetric phosphate neutralization. Science 1994, 266:1829-1834.
- [38]Kerppola TK, Curran T: The transcription activation domains of Fos and Jun induce DNA bending through electrostatic interactions. Embo J 1997, 16:2907-2916.
- [39]Li R, Knight J, Bream G, Stenlund A, Botchan M: Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes Dev 1989, 3:510-526.
- [40]Mistry N, Simonsson M, Evander M: Transcriptional activation of the human papillomavirus type 5 and 16 long control region in cells from cutaneous and mucosal origin. Virol J 2007, 4:27. BioMed Central Full Text
- [41]Sailaja G, Watts RM, Bernard HU: Many different papillomaviruses have low transcriptional activity in spite of strong epithelial specific enhancers. J Gen Virol 1999, 80(Pt 7):1715-1724.
- [42]McPhillips MG, Oliveira JG, Spindler JE, Mitra R, McBride AA: Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses. J Virol 2006, 80:9530-9543.