Human papillomaviruses: Basic mechanisms of pathogenesis and oncogenicity

Reviews in Medical Virology

Volumn 16, Issue 2, 2006, Pages 83-97

  Hebner, Christy M ^a   Laimins, Laimonis A ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN E1; GLYCOPROTEIN E2; UNCLASSIFIED DRUG; VIRUS E6 PROTEIN; VIRUS E7 PROTEIN; VIRUS PROTEIN; VIRUS VACCINE;

CARCINOGENESIS; CARCINOGENICITY; CELL CYCLE REGULATION; CELL DIFFERENTIATION; DNA VIRUS; EPITHELIUM CELL; INNATE IMMUNITY; LIFE CYCLE; NONHUMAN; PROTEIN FUNCTION; REVIEW; UTERINE CERVIX CARCINOMA; VIRUS PATHOGENESIS; VIRUS REPLICATION; WART VIRUS;

CAPSID PROTEINS; FEMALE; HUMANS; NEOPLASMS; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; TUMOR VIRUS INFECTIONS; VIRUS REPLICATION;

EID: 33645211201     PISSN: 10529276     EISSN: None     Source Type: Journal    
DOI: 10.1002/rmv.488     Document Type: Review

References (188)

1. Walboomers JM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 12-29.
2. zur Hausen H. Human papillomaviruses. Annu Rev Biochem 1994; 48: 427-447.
3. deVilliers EM. Human pathogenic papillomavirus types: an update. Curr Top Microbial Immunol 1994; 186: 1-12.
4. Koutsky LA. Epidemiology of genital human papillomavirus infection. Am J Med 1997; 102: 3-8.
5. Hildesheim A, et al. Persistence of type-specific human papillomavirus infection among cytologically normal women. J Infect Dis 1994; 169: 235-240.
6. Jenson AB, Kurman RJ, Lancaster WD. Tissue effects of and host response to human papillomavirus infection. Dermatol Clin 1991; 9: 203-209.
7. Parkin DM, et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94: 153-156.
8. Pecorelli S, et al. Cancer in women. Int J Gynaecol Obstet 2003; 82: 369-379.
9. Boring CC, et al. Cancer statistics 1994; CA Cancer J Clin 1994; 44: 7-26.
10. Pisani P, Bray F, Parkin DM. Estimates of the worldwide prevalence of cancer for 25 sites in the adult population. Int J Cancer 2002; 97: 72-81.
11. Singer A. Cervical cancer screening: state of the art. Baillieres Clin Obstet Gynaecol 1995; 9: 39-64.
12. Koutsky LA, et al. A Controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347: 1645-1651.
13. Howley PM. Papillomaviridae: the viruses and their replication. In Fundamental Virology, Howley PM (ed.). Lippincott-Raven Publishers: Philadelphia, PA, 1996; 947-978.
14. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical applications. Nat Rev Cancer 2002; 2: 342-350.
15. Monsonego J, et al. Cervical cancer control, priorities and new directions. Int J Cancer 2004; 108: 329-333.
16. Chen R, Aaltonen L-M, Vaheri A. Human papillomavirus type 16 in head and neck carcinogenesis. Rev Med Virol 2005, (Epub ahead of print). DOI:10.1002/rmv47.
17. Klumpp DJ, Laimins LA. Differentiation-induced changes in promoter usage for transcripts encoding the human papillomavirus type 31 replication protein E1. Virology 1999; 257: 239-246.
18. Ozbun M, Meyers C. Characterization of late gene transcripts expressed during vegetative replication of human papillomavirus type 31b. J Virol 1997; 71: 5161-5172.
19. Hummel M, Hudson JB, Laimins LA. Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes. J Virol 1992; 66: 6070-6080.
20. Ozbun MA, Meyers C. Human papillomavirus type 31b E1 and E2 transcript expression correlates with vegetative viral genome amplification. Virology 1998; 248: 218-230.
21. Morris PJ, et al. The octamer binding site in the HPV16 regulatory region produces opposite effects on gene expression in cervical and non-cervical cells. Nucleic Acids Res 1993; 21: 1019-1023.
22. Morris PJ, et al. Transactivation of the human papilloma virus 16 octamer motif by the octamer binding protein Oct-2 requires both the N and C terminal activation domains. Nucleic Acids Res 1993; 21: 4506-4510.
23. Tan SH, et al. The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID. J Virol 1994; 68: 6411-6420.
24. Kanaya T, Kyo S, Laimins LA. The 5′ region of the human papillomavirus type 31 upstream regulatory region acts as an enhancer which augments viral early expression through the action of YY1. Virology 1997; 237: 159-169.
25. Sen E, Alam S, Meyers C. Genetic and biochemical analysis of cis regulatory elements within the keratinocyte enhancer region of the human papillomavirus type 31 upstream regulatory region during different stages of the viral life cycle. J Virol 2004; 78: 612-629.
26. Frattini MG, Laimins LA. Binding of the human papillomavirus E1 origin-recognition protein is regulated through complex formation with the E2 enhancer-binding protein. Proc Natl Acad Sci USA 1994; 91: 12398-12402.
27. Ustav M, Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J 1991; 10: 449-457.
28. Watt FM. Epidermal stem cells: markers, patterning and the control of stem cell fate. Philos Trans R Soc Lond B Biol Sci 1998; 353: 831-837.
29. Stubenrauch F, Laimins LA. Human papillomavirus life cycle: active and latent phases. Semin Cancer Biol 1999; 9: 379-386.
30. Flores ER, et al. The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J Virol 2000; 74: 6622-6631.
31. Garner-Hamrick PA, et al. Global effects of human papillomavirus type 18 E6/E7 in an organotypic keratinocyte culture system. J Virol 2004; 78: 9041-9050.
32. Bouvard V, et al. Characterization of the human papillomavirus E2 protein: evidence of transactivation and trans-repression in cervical keratinocytes. EMBO J 1994; 13: 5451-5459.
33. Steger G, Corbach S. Dose-dependent regulation of the early promoter of human papillomavirus type 18 by the viral E2 protein. J Virol 1997; 71: 50-58.
34. Corden S, et al. The integration of HPV-18 DNA in cervical carcinoma. Mol Pathol 1999; 52: 275-282.
35. Jeon S, Allen-Hoffmann B, Lambert P. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 1995; 69: 2989-2997.
36. Thorland EC, et al. Common fragile sites are preferential targets for HPV16 integrations in cervical tumors. Oncogene 2003; 22: 1225-1237.
37. Cole ST, Danos O. Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome: phylogeny of papillomaviruses and repeated structure of the E6 and E7 gene products. J Mol Biol 1987; 193: 599-608.
38. Barbosa MS, Lowy DR, Schiller JT. Papillomavirus polypeptides E6 and E7 are zinc-binding proteins. J Virol 1989; 63: 1404-1407.
39. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10: 431-442.
40. Slee EA, O'Connor DJ, Lu X. To die or not to die: how does p53 decide? Oncogene 2004; 23: 2809-2818.
41. Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 1990; 248: 76-79.
42. Scheffner M, et al. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990; 63: 1129-1136.
43. Huibregtse JM, Scheffner M, Howley PM. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J 1991; 10: 4129-4135.
44. Thomas MC, Chiang CM. E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation. Mol Cell 2005; 17: 251-264.
45. Patel D, et al. The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. EMBO J 1999; 18: 5061-5072.
46. Zimmermann H, et al. The human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300. J Virol 1999; 73: 6209-6219.
47. Kim SK. Polarized signaling: basolateral receptor localization in epithelial cells by PDZ-containing proteins. Curr Opin Cell Biol 1997; 9: 853-859.
48. Kiyono T, et al. Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci USA 1997; 94: 11612-11616.
49. Gardiol D, et al. Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 1999; 18: 5487-5496.
50. Thomas M, et al. Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation. Oncogene 2002; 21: 5088-5096.
51. Nakagawa S, Huibregtse JM. Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 2000; 20: 8244-8253.
52. Lee SS, et al. Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. J Virol 2000; 74: 9680-9693.
53. Lee C, Laimins LA. Role of the PDZ domain-binding motif of the oncoprotein E6 in the pathogenesis of human papillomavirus type 31. J Virol 2004; 78: 12366-12377.
54. Favre-Bonvin A, et al. Human papillomavirus type 18 E6 protein binds the cellular PDZ protein TIP-2/GIPC, which is involved in transforming growth factor beta signaling and triggers its degradation by the proteasome. J Virol 2005; 79: 4229-4237.
55. Massimi P, et al. HPV E6 specifically targets different cellular pools of its PDZ domain-containing tumour suppressor substrates for proteasome-mediated degradation. Oncogene 2004; 23: 8033-8039.
56. Nguyen ML, et al. The PDZ ligand domain f human papillomavirus type 16 E6 protein is required for E6's induction of epithelial hyperplasia in vivo. J Virol 2003; 77: 6957-6964.
57. Nguyen MM, et al. Requirement of PDZ-containing proteins for cell cycle regulation and differentiation in the mouse lens epithelium. Mol Cell Biol 2003; 23: 8970-8981.
58. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 1996; 380: 79-82.
59. Stoppler H, et al. The human papillomavirus type 16 E6 and E7 oncoproteins dissociate cellular telomerase activity from the maintenance of telomere length. J Biol Chem 1997; 272: 13332-13337.
60. Veldman T, et al. Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16 E6 oncoprotein. J Virol 2001; 75: 4467-4472.
61. Gewin L, Galloway DA. E box-dependent activation of telomerase by human papillomavirus type 16 E6 does not require induction of c-myc. J Virol 2001; 75: 7198-7201.
62. Oh ST, Kyo S, Laimins LA. Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Sp1 binding sites. J Virol 2001; 75: 5559-5566.
63. Veldman T, et al. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci USA 2003; 100: 8211-8216.
64. Kiyono T, et al. Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 1998; 396: 84-88.
65. Barbosa MS, et al. The region of the HPV E7 oncoprotein homologous to adenovirus E1a and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation. EMBO J 1990; 9: 153-160.
66. Dyson N, et al. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J Virol 1992; 66: 6893-6902.
67. Chellappan S, et al. Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci USA 1992; 89: 4549-4553.
68. Massimi P, Banks L. Differential phosphorylation of the HPV-16 E7 oncoprotein during the cell cycle. Virology 2000; 276: 388-394.
69. Tugizov S, et al. Inhibition of human papillomavirus type 16 E7 phosphorylation by the S100 MRP-8/14 protein complex. J Virol 2005; 79: 1099-1112.
70. Jones DL, Thompson DA, Munger K. Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis. Virology 1997; 239: 97-107.
71. Boyer SN, Wazer DE, Band V. E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Cancer Res 1996; 56: 4620-4624.
72. Berezutskaya E, et al. Differential regulation of the pocket domains of the retinoblastoma family proteins by the HPV16 E7 oncoprotein. Cell Growth Differ 1997; 8: 1277-1286.
73. Huang PS, et al. Protein domains governing interactions between E2F, the retinoblastoma gene product, and human papillomavirus type 16 E7 protein. Mol Cell Biol 1993; 13: 953-960.
74. Patrick DR, Oliff A, Heimbrook DC. Identification of a novel retinoblastoma gene product binding site on human papillomavirus type 16 E7 protein. J Biol Chem 1994; 269: 6842-6850.
75. Nguyen DX, Westbrook TF, McCance DJ. Human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest. J Virol 2002; 76: 619-632.
76. Phelps WC, et al. Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. J Virol 1992; 66: 2418-2427.
77. Gonzalez SL, et al. Degradation of the retinoblastoma tumor suppressor by the human papillomavirus type 16 E7 oncoprotein is important for functional inactivation and is separable from proteasomal degradation of E7. J Virol 2001; 75: 7583-7591.
78. Schmitt A, et al. Comparison of the properties of the E6 and E7 genes of low- and high-risk cutaneous papillomaviruses reveals strongly transforming and high Rb-binding activity for the E7 protein of the low-risk human papillomavirus type 1. J Virol 1994; 68: 7051-7059.
79. Longworth MS, Laimins LA. The binding of histone deacetylases and the integrity of zinc finger-like motifs of the E7 protein are essential for the life cycle of human papillomavirus type 31. J Virol 2004; 78: 3533-3541.
80. Brehm A, et al. The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J 1999; 18: 2449-2458.
81. Longworth MS, Wilson R, Laimins LA. HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs. EMBO J 2005; 24: 1821-1830.
82. Hwang SG, et al. Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner. J Biol Chem 2002; 277: 2923-2930.
83. Tommasino M, et al. HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A. Oncogene 1993; 8: 195-202.
84. McIntyre MC, Ruesch MN, Laimins LA. Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex with cdk2 and p107. Virology 1996; 215: 73-82.
85. Ruesch MN, Laimins LA. Human papillomavirus oncoproteins alter differentiation-dependent cell cycle exit on suspension in semisolid medium. Virology 1998; 250: 19-29.
86. Zerfass-Thome K, et al. Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene 1996; 13: 2323-2330.
87. Funk JO, et al. Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Genes Dev 1997; 11: 2090-2100.
88. Duensing S, et al. The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci USA 2000; 97: 10002-10007.
89. Duensing S, et al. Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. J Virol 2001; 75: 7712-7716.
90. Southern SA, et al. Tetrasomy is induced by human papillomavirus type 18 E7 gene expression in keratinocyte raft cultures. Cancer Res 2001; 61: 4858-4863.
91. Duensing S, Munger K. Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members. J Virol 2003; 77: 12331-12335.
92. Chiang CM, et al. Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc Natl Acad Sci USA 1992; 89: 5799-5803.
93. Sverdrup F, Khan SA. Replication of human papillomavirus (HPV) DNAs supported by the HPV type 18 E1 and E2 proteins. J Virol 1994; 68: 505-509.
94. Danos O, et al. Comparative analysis of the human type 1a and bovine type 1 papillomavirus genomes. J Virol 1983; 46: 557-566.
95. Danos O, Katinka M, Yaniv M. Human papillomavirus 1a complete DNA sequence: a novel type of genome organization among papovaviridae. EMBO J 1982; 1: 231-236.
96. Raj K, Stanley MA. The ATP-binding and ATPase activities of human papillomavirus type 16 E1 are significantly weakened by the absence of prolines in its ATP-binding domain. J Gen Virol 1995; 76: 2949-2956.
97. Hughes FJ, Romanos MA. E1 protein of human papillomavirus is a DNA helicase/ATPase. Nucleic Acids Res 1993; 21: 5817-5823.
98. Conger KL, et al. Human papillomavirus DNA replication. Interactions between the viral E1 protein and two subunits of human dna polymerase alpha/primase. J Biol Chem 1999; 274: 2696-2705.
99. Masterson PJ, et al. A C-terminal helicase domain of the human papillomavirus E1 protein binds E2 and the DNA polymerase alpha-primase p68 subunit. J Virol 1998; 72: 7407-7419.
100. Frattini MG, Laimins LA. The role of the E1 and E2 proteins in the replication of human papillomavirus type 31b. Virology 1994; 204: 799-804.
101. Kuo SR, et al. Cell-free replication of the human papillomavirus DNA with homologous viral E1 and E2 proteins and human cell extracts. J Biol Chem 1994; 269: 24058-24065.
102. Lusky M, Hurwitz J, Seo YS. Cooperative assembly of the bovine papilloma virus E1 and E2 proteins on the replication origin requires an intact E2 binding site. J Biol Chem 1993; 268: 15795-15803.
103. Mohr IJ, et al. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 1990; 250: 1694-1699.
104. Sanders CM, Stenlund A. Transcription factor-dependent loading of the E1 initiator reveals modular assembly of the papillomavirus origin melting complex. J Biol Chem 2000; 275: 3522-3534.
105. Sedman T, Sedman J, Stenlund A. Binding of the E1 and E2 proteins to the origin of replication of bovine papillomavirus. J Virol 1997; 71: 2887-2896.
106. Sedman J, Stenlund A. The papillomavirus E1 protein forms a DNA-dependent hexameric complex with ATPase and DNA helicase activities. J Virol 1998; 72: 6893-6897.
107. Liu JS, et al. Human Hsp70 and Hsp40 chaperone proteins facilitate human papillomavirus-11 E1 protein binding to the origin and stimulate cell-free DNA replication. J Biol Chem 1998; 273: 30704-30712.
108. Loo YM, Melendy T. Recruitment of replication protein A by the papillomavirus E1 protein and modulation by single-stranded DNA. J Virol 2004; 78: 1605-1615.
109. Ma T, et al. Interaction between cyclin-dependent kinases and human papillomavirus replication-initiation protein E1 is required for efficient viral replication. Proc Natl Acad Sci USA 1999; 96: 382-387.
110. Deng W, et al. Cyclin/CDK regulates the nucleocytoplasmic localization of the human papillomavirus E1 DNA helicase. J Virol 2004; 78: 13954-13965.
111. Antson AA, et al. Structure of the intact transactivation domain of the human papillomavirus E2 protein. Nature 2000; 403: 805-809.
112. Kim SS, et al. The structural basis of DNA target discrimination by papillomavirus E2 proteins. J Biol Chem 2000; 275: 31245-31254.
113. Hegde RS, et al. Crystal structure at 1.7 A of the bovine papillomavirus-1 E2 DMA-binding domain bound to its DNA target. Nature 1992; 359: 505-512.
114. McBride AA, Romanczuk H, Howley PM. The papillomavirus E2 regulatory proteins. J Biol Chem 1991; 266: 18411-18414.
115. Pett MR, et al. Acquisition of high-level chromosomal instability is associated with integration of human papillomavirus type 16 in cervical keratinocytes. Cancer Res 2004; 64: 1359-1368.
116. Lee D, et al. cAMP response element-binding protein-binding protein binds to human papillomavirus E2 protein and activates E2-dependent transcription. J Biol Chem 2000; 275: 7045-7051.
117. Lee D, et al. Functional interaction between p/CAF and human papillomavirus E2 protein. J Biol Chem 2002; 277: 6483-6489.
118. Demeret C, Yaniv M, Thierry F. The E2 transcriptional repressor can compensate for Sp1 activation of the human papillomavirus type 18 early promoter. J Virol 1994; 68: 7075-7082.
119. Dong G, Broker TR, Chow LT. Human papillomavirus type 11 E2 proteins repress the homologous E6 promoter by interfering with the binding of host transcription factors to adjacent elements. J Virol 1994; 68: 1115-1127.
120. 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.
121. Hadaschik D, et al. The Papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation. J Virol 2003; 77: 5253-5265.
122. Baxter MK, et al. The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4. J Virol 2005; 79: 4806-4818.
123. You J, et al. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 2004; 117: 349-360.
124. Doorbar J, et al. Identification of the human papilloma virus-1a E4 gene products. EMBO J 1986; 5: 355-362.
125. Nasseri M, et al. A human papilloma virus type 11 transcript encoding an E1-E4 protein. Virology 1987; 159: 433-439.
126. Doorbar J, et al. Characterization of events during the late stages of HPV16 infection in vivo using high-affinity synthetic Fabs to E4. Virology 1997; 238: 40-52.
127. Middleton K, et al. Organization of human papillomavirus productive cycle during neoplastic progression provides a basis for selection of diagnostic markers. J Virol 2003; 77: 10186-10201.
128. Peh WL, et al. Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol 2002; 76: 10401-10416.
129. Pray TR, Laimins LA. Differentiation-dependent expression of E1-E4 proteins in cell lines maintaining episomes of human papillomavirus type 31b. Virology 1995; 206: 679-685.
130. Wang Q, et al. Functional analysis of the human papillomavirus type 16 E1=E4 protein provides a mechanism for in vivo and in vitro keratin filament reorganization. J Virol 2004; 78: 821-833.
131. Roberts S, et al. Mutational analysis of the human papillomavirus type 16 E1-E4 protein shows that the C terminus is dispensable for keratin cytoskeleton association but is involved in inducing disruption of the keratin filaments. J Virol 1997; 71: 3554-3562.
132. Sterling JC, Skepper JN, Stanley MA. Immunoelectron microscopical localization of human papillomavirus type 16 L1 and E4 proteins in cervical keratinocytes cultured in vivo. J Invest Dermatol 1993; 100: 154-158.
133. Roberts S, et al. Mutational analysis of human papillomavirus E4 proteins: identification of structural features important in the formation of cytoplasmic E4/cytokeratin networks in epithelial cells. J Virol 1994; 68: 6432-6445.
134. Doorbar J, et al. Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature 1991; 352: 824-827.
135. Roberts S, et al. Cutaneous and mucosal human papillomavirus E4 proteins form intermediate filament-like structures in epithelial cells. Virology 1993; 197: 176-187.
136. Doorbar J, Medcalf E, Napthine S. Analysis of HPV1 E4 complexes and their association with keratins in vivo. Virology 1996; 218: 114-126.
137. Palefsky JM, et al. Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. J Clin Invest 1991; 87: 2132-2141.
138. Wilson R, Fehrmann F, Laimins LA. Role of the E1-E4 protein in the differentiation-dependent life cycle of human papillomavirus type 31. J Virol 2005; 79: 6732-6740.
139. 2 arrest is associated with cytoplasmic retention of active Cdk1/cyclin B1 complexes. J Virol 2005; 79: 3998-4011.
140. Davy CE, et al. Identification of a G(2) arrest domain in the E1 wedge E4 protein of human papillomavirus type 16. J Virol 2002; 76: 9806-9818.
141. Nakahara T, et al. Modulation of the cell division cycle by human papillomavirus type 18 E4. J Virol 2002; 76: 10914-10920.
142. Doorbar J, et al. The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus. J Virol 2000; 74: 10081-10095.
143. Conrad M, Bubb VJ, Schlegel R. The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein. J Virol 1993; 67: 6170-6178.
144. Burkhardt A, et al. The E5 oncoprotein of bovine papillomavirus is oriented asymmetrically in Golgi and plasma membranes. Virology 1989; 170: 334-339.
145. Valle GF, Banks L. The human papillomavirus (HPV)-6 and HPV-16 E5 proteins co-operate with HPV-16 E7 in the transformation of primary rodent cells. J Gen Virol 1995; 76: 1239-1245.
146. Bouvard V, et al. The human papillomavirus type 16 E5 gene cooperates with the E7 gene to stimulate proliferation of primary cells and increases viral gene expression. Virology 1994; 203: 73-80.
147. Conrad M, Bubb VJ, Schlegel R. The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein. J Virol 1993; 67: 6170-6178.
148. Hwang ES, Nottoli T, Dimaio D. The HPV16 E5 protein: expression, detection, and stable complex formation with transmembrane proteins in COS cells. Virology 1995; 211: 227-233.
149. Straight SW, et al. The E5 oncoprotein of human papillomavirus type 16 transforms fibroblasts and effects the downregulation of the epidermal growth factor receptor in keratinocytes. J Virol 1993; 67: 4521-4532.
150. Crusius K, Auvinen E, Alonso A. Enhancement of EGF- and PMA-mediated MAP kinase activation in cells expressing the human papillomavirus type 16 E5 protein. Oncogene 1997; 15: 1437-1444.
151. Crusius K, et al. The human papillomavirus type 16 E5-protein modulates ligand-dependent activation of the EGF receptor family in the human epithelial cell line HaCaT. Exp Cell Res 1998; 241: 76-83.
152. Zhang B, Spandau DF, Roman A. E5 protein of human papillomavirus Type 16 protects human foreskin keratinocytes from UV B-irradiation-induced apoptosis. J Virol 2002; 76: 220-231.
153. Gu Z, Matlashewski G. Effect of human papillomavirus type 16 oncogenes on MAP kinase activity. J Virol 1995; 69: 8051-8056.
154. Disbrow GL, Hanover JA, Schlegel R. Endoplasmic reticulum-localized human papillomavirus type 16 E5 protein alters endosomal pH but not trans-Golgi pH. J Virol 2005; 79: 5839-5846.
155. Straight SW, Herman B, McCance DJ. The E5 oncoprotein of human papillomavirus type 16 inhibits the acidification of endosomes in human keratinocytes. J Virol 1995; 69: 3185-3192.
156. Thomsen P, et al. The HPV16 E5 oncogene inhibits endocytic trafficking. Oncogene 2000; 19: 6023-6032.
157. Ashrafi GH, et al. E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I. Int J Cancer 2005; 113: 276-283.
158. Zhang B, et al. The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-gamma. Virology 2003; 310: 100-108.
159. Fehrmann F, Klumpp DJ, Laimins LA. Human papillomavirus type 31 E5 protein supports cell cycle progression and activates late viral functions upon epithelial differentiation. J Virol 2003; 77: 2819-2831.
160. Genther SM, et al. Quantitative role of the human papillomavirus type 16 E5 gene during the productive stage of the viral life cycle. J Virol 2003; 77: 2832-2842.
161. Chen XS, et al. Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell 2000; 5: 557-567.
162. Modis Y, Trus BL, Harrison SC Atomic model of the papillomavirus capsid. EMBO J 2002; 21: 4754-4762.
163. Becker KA, et al. Nuclear localization but not PML protein is required for incorporation of the papillomavirus minor capsid protein L2 into virus-like particles. J Virol 2004; 78: 1121-1128.
164. Trus BL, et al. Novel structural features of bovine papillomavirus capsid revealed by a three-dimensional reconstruction to 9 A resolution. Nat Struct Biol 1997; 4: 413-420.
165. Swindle CS, et al. Human papillomavirus DNA replication compartments in a transient DNA replication system. J Virol 1999; 73: 1001-1009.
166. Paintsil J, et al. Carboxyl terminus of bovine papillomavirus type-1 L1 protein is not required for capsid formation. Virology 1996; 223: 238-244.
167. Sapp M, et al. Organization of the major and minor capsid proteins in human papillomavirus type 33 virus-like particles. J Gen Virol 1995; 76: 2407-2412.
168. Finnen RL, et al. Interactions between papillomavirus L1 and L2 capsid proteins. J Virol 2003; 77: 4818-4826.
169. Buck CB, et al. Maturation of papillomavirus capsids. J Virol 2005; 79: 2839-2846.
170. Nelson LM, Rose RC, Moroianu J. Nuclear import strategies of high risk HPV16 L1 major capsid protein. J Biol Chem 2002; 277: 23958-23964.
171. Darshan MS, et al. The 12 minor capsid protein of human papillomavirus type 16 interacts with a network of nuclear import receptors. J Virol 2004; 78: 12179-12188.
172. Zhou J, et al. Interaction of human papillomavirus (HPV) type 16 capsid proteins with HPV DNA requires an intact L2 N-terminal sequence. J Virol 1994; 68: 619-625.
173. Day PM, et al. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. PNAS 2004; 101: 14252-14257.
174. Florin L, et al. Reorganization of nuclear domain 10 induced by papillomavirus capsid protein 12. Virology 2002; 295: 97-107.
175. Natale C, et al. Computer-assisted analysis of molecular mimicry between human papillomavirus 16 E7 oncoprotein and human protein sequences. Immunol Cell Biol 2000; 78: 580-585.
176. al-Saleh W, et al. Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix. J Pathol 1998; 184: 283-290.
177. Clerici M, et al. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. J Natl Cancer Inst 1997; 89: 245-250.
178. Malmgaard L, Induction and Regulation of IFNs during viral infections. J Interferon Cytokine Res 2004; 24: 439-454.
179. Barber GN. Host defense, viruses and apoptosis. Cell Death Differ 2001; 8: 113-126.
180. Stark GR, et al. How cells respond to interferons. Annu Rev Biochem 1998; 67: 227-264.
181. Brierley MM, Fish EN. Review: IFN-alpha/beta receptor interactions to biologic outcomes: understanding the circuitry. J Interferon Cytokine Res 2002; 22: 835-845.
182. Nees M, et al. Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes. J Virol 2001; 75: 4283-4296.
183. Chang YE, Laimins LA. Microarray analysis identifies interferon-inducible genes and Stat-1 as major transcriptional targets of human papillomavirus type 31. J Virol 2000; 74: 4174-4182.
184. Ronco LV, et al. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 1998; 12: 2061-2072.
185. Park JS, et al. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein: implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem 2000; 275: 6764-6769.
186. Um SJ, et al. Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo. Cancer Lett 2002; 179: 205-212.
187. Barnard P, McMillan NA. The human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alpha. Virology 1999; 259: 305-313.
188. Kazemi S, et al. Control of alpha subunit of eukaryotic translation initiation factor 2 (eIF2 alpha) phosphorylation by the human papillomavirus type 18 E6 oncoprotein: implications for eIF2 alpha-dependent gene expression and cell death. Mol Cell Biol 2004; 24: 3415-3429.