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Human Papillomaviruses

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Cancers in People with HIV and AIDS

Abstract

Human papillomaviruses (HPV) are a family of small DNA tumor viruses with a size of ~52–55. The family consists of ~200 different genotypes; many of the types cause benign warts or papilloma, while a small fraction of oncogenic or “high-risk” types can cause invasive cervical cancer or other tumors. HPV infects keratinocytes in the basal layer of stratified squamous epithelia and replicates in the nucleus of infected keratinocytes along with keratinocyte differentiation. The viral genome in size of ~7.9 kb encodes six early, non-structural regulatory proteins (E1, E2, E4, E5, E6, and E7) and two late structural proteins (L1 and L2). E6 and E7 are two oncoproteins responsible for the viral oncogenesis of high-risk HPVs, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82. L1 is a major structural component of viral capsid and its self-assembly in vitro into a viral-like particle (VLP) provides the basis of prophylactic vaccines against infections of several HPV types. In addition to cervical cancer, high-risk HPVs are associated with the development of various anogenital cancers and certain head and neck cancers.

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References

  • Abbate EA, Berger JM, Botchan MR. The X-ray structure of the papillomavirus helicase in complex with its molecular matchmaker E2. Genes Dev. 2004;18:1981–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Abbate EA, Voitenleitner C, Botchan MR. Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association. Mol Cell. 2006;24: 877–89.

    CAS  PubMed  Google Scholar 

  • Androphy EJ, Lowy DR, Schiller JT. Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature. 1987;325:70–3.

    CAS  PubMed  Google Scholar 

  • Avvakumov N, Torchia J, Mymryk JS. Interaction of the HPV E7 proteins with the pCAF acetyltransferase. Oncogene. 2003;22:3833–41.

    CAS  PubMed  Google Scholar 

  • Bagarazzi ML et al. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med. 2012;4:155ra138.

    PubMed  Google Scholar 

  • Bechtold V, Beard P, Raj K. Human papillomavirus type 16 E2 protein has no effect on transcription from episomal viral DNA. J Virol. 2003;77:2021–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bell I, Martin A, Roberts S. The E1circumflexE4 protein of human papillomavirus interacts with the serine-arginine-specific protein kinase SRPK1. J Virol. 2007;81:5437–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ben KY et al. The human papillomavirus E6 oncogene represses a cell adhesion pathway and disrupts focal adhesion through degradation of TAp63beta upon transformation. PLoS Pathog. 2011;7:e1002256.

    Google Scholar 

  • Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010;401:70–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bernat A, Avvakumov N, Mymryk JS, Banks L. Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300. Oncogene. 2003;22:7871–81.

    PubMed  Google Scholar 

  • Bienkowska-Haba M, Williams C, Kim SM, Garcea RL, Sapp M. Cyclophilins facilitate dissociation of the human papillomavirus type 16 capsid protein L1 from the L2/DNA complex following virus entry. J Virol. 2012;86:9875–87.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bishop B et al. Crystal structures of four types of human papillomavirus L1 capsid proteins: understanding the specificity of neutralizing monoclonal antibodies. J Biol Chem. 2007;282:31803–11.

    CAS  PubMed  Google Scholar 

  • Blachon S, Bellanger S, Demeret C, Thierry F. Nucleo-cytoplasmic shuttling of high risk human Papillomavirus E2 proteins induces apoptosis. J Biol Chem. 2005;280:36088–98.

    CAS  PubMed  Google Scholar 

  • Bodaghi S, Jia R, Zheng ZM. Human papillomavirus type 16 E2 and E6 are RNA-binding proteins and inhibit in vitro splicing of pre-mRNAs with suboptimal splice sites. Virology. 2009;386(1):32–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bonagura VR et al. Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11. APMIS. 2010;118:455–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bottley G, Watherston OG, Hiew YL, Norrild B, Cook GP, Blair GE. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells. Oncogene. 2008;27:1794–9.

    CAS  PubMed  Google Scholar 

  • Bousarghin L, Touze A, Combita-Rojas AL, Coursaget P. Positively charged sequences of human papillomavirus type 16 capsid proteins are sufficient to mediate gene transfer into target cells via the heparan sulfate receptor. J Gen Virol. 2003;84:157–64.

    CAS  PubMed  Google Scholar 

  • Bronnimann MP, Chapman JA, Park CK, Campos SK. A transmembrane domain and GxxxG motifs within L2 are essential for papillomavirus infection. J Virol. 2013;87:464–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buck CB et al. Arrangement of L2 within the papillomavirus capsid. J Virol. 2008;82:5190–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Campo MS et al. HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology. 2010;407:137–42.

    CAS  PubMed  Google Scholar 

  • Chaturvedi AK et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294–301.

    PubMed Central  PubMed  Google Scholar 

  • Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC. Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell. 2000;5:557–67.

    CAS  PubMed  Google Scholar 

  • Coleman N et al. Immunological events in regressing genital warts. Am J Clin Pathol. 1994;102:768–74.

    CAS  PubMed  Google Scholar 

  • Cote-Martin A et al. Human papillomavirus E1 helicase interacts with the WD repeat protein p80 to promote maintenance of the viral genome in keratinocytes. J Virol. 2008;82:1271–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Crequer A et al. Inherited MST1 deficiency underlies susceptibility to EV-HPV infections. PLoS One. 2012a;7:e44010.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Crequer A et al. Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections. J Clin Invest. 2012b;122:3239–47.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Crow JM. HPV: the global burden. Nature. 2012;488:S2–3.

    PubMed  Google Scholar 

  • Danos O, Katinka M, Yaniv M. Human papillomavirus 1a complete DNA sequence: a novel type of genome organization among papovaviridae. EMBO J. 1982;1:231–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dasgupta J et al. Structural basis of oligosaccharide receptor recognition by human papillomavirus. J Biol Chem. 2011;286:2617–24.

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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;76:9806–18.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Day PM, Baker CC, Lowy DR, Schiller JT. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. Proc Natl Acad Sci U S A. 2004;101:14252–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • de Sanjose S et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11:1048–56.

    PubMed  Google Scholar 

  • de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324:17–27.

    PubMed  Google Scholar 

  • DeFilippis RA, Goodwin EC, Wu L, DiMaio D. Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells. J Virol. 2003;77:1551–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Desaintes C, Hallez S, Van Alphen P, Burny A. Transcriptional activation of several heterologous promoters by the E6 protein of human papillomavirus type 16. J Virol. 1992;66:325–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Donovan B et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis. 2011;11:39–44.

    PubMed  Google Scholar 

  • Doorbar J et al. Detection of novel splicing patterns in a HPV16-containing keratinocyte cell line. Virology. 1990;178:254–62.

    CAS  PubMed  Google Scholar 

  • Doorbar J, Ely S, Sterling J, McLean C, Crawford L. Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature. 1991;352:824–7.

    CAS  PubMed  Google Scholar 

  • 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;74:10081–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 U S A. 2000;97:10002–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dunne EF et al. Prevalence of HPV infection among females in the United States. JAMA. 2007;297:813–9.

    CAS  PubMed  Google Scholar 

  • Durst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A. 1983;80:3812–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dziduszko A, Ozbun MA. Annexin A2 and S100A10 regulate human papillomavirus type 16 entry and intracellular trafficking in human keratinocytes. J Virol. 2013;87:7502–15.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Egawa N et al. The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome. J Virol. 2012;86:3276–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ehehalt D et al. Detection of human papillomavirus type 18 E7 oncoprotein in cervical smears: a feasibility study. J Clin Microbiol. 2012;50:246–57.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fausch SC, Da Silva DM, Rudolf MP, Kast WM. Human papillomavirus virus-like particles do not activate Langerhans cells: a possible immune escape mechanism used by human papillomaviruses. J Immunol. 2002;169:3242–9.

    CAS  PubMed  Google Scholar 

  • Finnen RL, Erickson KD, Chen XS, Garcea RL. Interactions between papillomavirus L1 and L2 capsid proteins. J Virol. 2003;77:4818–26.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Flores ER, Lambert PF. Evidence for a switch in the mode of human papillomavirus type 16 DNA replication during the viral life cycle. J Virol. 1997;71:7167–79.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fradet-Turcotte A, Bergeron-Labrecque F, Moody CA, Lehoux M, Laimins LA, Archambault J. Nuclear accumulation of the papillomavirus E1 helicase blocks S-phase progression and triggers an ATM-dependent DNA damage response. J Virol. 2011;85:8996–9012.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Freitas AC, Mariz FC, Silva MA, Jesus AL. Human papillomavirus vertical transmission: review of current data. Clin Infect Dis. 2013;56:1451–6.

    CAS  PubMed  Google Scholar 

  • French D et al. Expression of HPV16 E5 down-modulates the TGFbeta signaling pathway. Mol Cancer. 2013;12:38.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frisch M et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997;337:1350–8.

    CAS  PubMed  Google Scholar 

  • Ganguly N. Human papillomavirus-16 E5 protein: oncogenic role and therapeutic value. Cell Oncol (Dordr). 2012;35:67–76.

    CAS  Google Scholar 

  • Geimanen J et al. Development of a cellular assay system to study the genome replication of high- and low-risk mucosal and cutaneous human papillomaviruses. J Virol. 2011;85: 3315–29.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gillison ML et al. Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis. Vaccine. 2012;30 Suppl 5:F34–54.

    PubMed  Google Scholar 

  • Griffin H et al. E4 antibodies facilitate detection and type-assignment of active HPV infection in cervical disease. PLoS One. 2012;7:e49974.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haverkos HW, Soon G, Steckley SL, Pickworth W. Cigarette smoking and cervical cancer: Part I: a meta-analysis. Biomed Pharmacother. 2003;57:67–77.

    PubMed  Google Scholar 

  • Hawley-Nelson P, Androphy EJ, Lowy DR, Schiller JT. The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. EMBO J. 1988;7:525–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ho GY, Studentsov YY, Bierman R, Burk RD. Natural history of human papillomavirus type 16 virus-like particle antibodies in young women. Cancer Epidemiol Biomarkers Prev. 2004;13:110–6.

    CAS  PubMed  Google Scholar 

  • Hoskins EE et al. The fanconi anemia pathway limits human papillomavirus replication. J Virol. 2012;86:8131–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang SM, McCance DJ. Down regulation of the interleukin-8 promoter by human papillomavirus type 16 E6 and E7 through effects on CREB binding protein/p300 and P/CAF. J Virol. 2002;76:8710–21.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huh K et al. Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor. J Virol. 2007;81:9737–47.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huibregtse JM, Scheffner M, Howley PM. Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol Cell Biol. 1993;13:775–84.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iannacone MR et al. Case-control study of cutaneous human papillomavirus infection in Basal cell carcinoma of the skin. J Invest Dermatol. 2013;133:1512–20.

    CAS  PubMed  Google Scholar 

  • Imai Y, Tsunokawa Y, Sugimura T, Terada M. Purification and DNA-binding properties of human papillomavirus type 16 E6 protein expressed in Escherichia coli. Biochem Biophys Res Commun. 1989;164:1402–10.

    CAS  PubMed  Google Scholar 

  • Jabbar SF et al. Cervical cancers require the continuous expression of the human papillomavirus type 16 E7 oncoprotein even in the presence of the viral E6 oncoprotein. Cancer Res. 2012;72:4008–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jackson S, Harwood C, Thomas M, Banks L, Storey A. Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Genes Dev. 2000;14:3065–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jagu S et al. Optimization of multimeric human papillomavirus L2 vaccines. PLoS One. 2013a;8:e55538.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jagu S et al. Phylogenetic considerations in designing a broadly protective multimeric L2 vaccine. J Virol. 2013b;87:6127–36.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jia R et al. Control of the papillomavirus early-to-late switch by differentially expressed SRp20. J Virol. 2009;83:167–80.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Johansson C et al. HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting early polyadenylation. EMBO J. 2012;31:3212–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kenter GG et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med. 2009;361:1838–47.

    CAS  PubMed  Google Scholar 

  • Khan J et al. Role of calpain in the formation of human papillomavirus type 16 E1^E4 amyloid fibers and reorganization of the keratin network. J Virol. 2011;85:9984–97.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim SH et al. Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ ERK1,2 and PI3K/Akt. Cell Mol Life Sci. 2006;63:930–8.

    CAS  PubMed  Google Scholar 

  • Kiyono T, Hiraiwa A, Fujita M, Hayashi Y, Akiyama T, Ishibashi M. Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A. 1997;94:11612–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klaes R et al. Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer. 2001;92:276–84.

    CAS  PubMed  Google Scholar 

  • Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature. 1996;380:79–82.

    CAS  PubMed  Google Scholar 

  • Koshiol JE et al. Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus. Int J Cancer. 2006;119:1623–9.

    CAS  PubMed  Google Scholar 

  • Krawczyk E et al. Koilocytosis: a cooperative interaction between the human papillomavirus E5 and E6 oncoproteins. Am J Pathol. 2008;173:682–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krawczyk E, Suprynowicz FA, Sudarshan SR, Schlegel R. Membrane orientation of the human papillomavirus type 16 E5 oncoprotein. J Virol. 2010;84:1696–703.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kreimer AR et al. Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol. 2013;31:2708–15.

    PubMed  Google Scholar 

  • Kumar A et al. Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Mol Cell Biol. 2002;22:5801–12.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kusumoto-Matsuo R, Kanda T, Kukimoto I. Rolling circle replication of human papillomavirus type 16 DNA in epithelial cell extracts. Genes Cells. 2011;16:23–33.

    CAS  PubMed  Google Scholar 

  • Lai MC, Teh BH, Tarn WY. A human papillomavirus E2 transcriptional activator. The interactions with cellular splicing factors and potential function in pre-mRNA processing. J Biol Chem. 1999;274:11832–41.

    CAS  PubMed  Google Scholar 

  • Lee SS, Weiss RS, Javier RT. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A. 1997;94:6670–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee JO, Russo AA, Pavletich NP. Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature. 1998;391:859–65.

    CAS  PubMed  Google Scholar 

  • Lehoux M, Fradet-Turcotte A, Lussier-Price M, Omichinski JG, Archambault J. Inhibition of human papillomavirus DNA replication by an E1-derived p80/UAF1-binding peptide. J Virol. 2012;86:3486–500.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li M, Cripe TP, Estes PA, Lyon MK, Rose RC, Garcea RL. Expression of the human papillomavirus type 11 L1 capsid protein in Escherichia coli: characterization of protein domains involved in DNA binding and capsid assembly. J Virol. 1997;71:2988–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li S et al. The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene. 1999;18:5727–37.

    CAS  PubMed  Google Scholar 

  • Li H, Ou X, Xiong J, Wang T. HPV16E7 mediates HADC chromatin repression and downregulation of MHC class I genes in HPV16 tumorigenic cells through interaction with an MHC class I promoter. Biochem Biophys Res Commun. 2006;349:1315–21.

    CAS  PubMed  Google Scholar 

  • Lichtig H et al. HPV16 E6 augments Wnt signaling in an E6AP-dependent manner. Virology. 2010;396:47–58.

    CAS  PubMed  Google Scholar 

  • Lidqvist M et al. Detection of human papillomavirus oncoprotein E7 in liquid-based cytology. J Gen Virol. 2012;93:356–63.

    CAS  PubMed  Google Scholar 

  • Lipovsky A et al. Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus. Proc Natl Acad Sci U S A. 2013;110:7452–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Massad LS et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121:829–46.

    PubMed  Google Scholar 

  • Massimi P, Pim D, Banks L. Human papillomavirus type 16 E7 binds to the conserved carboxy-terminal region of the TATA box binding protein and this contributes to E7 transforming activity. J Gen Virol. 1997;78(Pt 10):2607–13.

    CAS  PubMed  Google Scholar 

  • Maufort JP, Shai A, Pitot HC, Lambert PF. A role for HPV16 E5 in cervical carcinogenesis. Cancer Res. 2010;70:2924–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  • McBride AA. Replication and partitioning of papillomavirus genomes. Adv Virus Res. 2008;72: 155–205.

    CAS  PubMed Central  PubMed  Google Scholar 

  • McLaughlin-Drubin ME, Munger K. The human papillomavirus E7 oncoprotein. Virology. 2009;384:335–44.

    CAS  PubMed Central  PubMed  Google Scholar 

  • McLaughlin-Drubin ME, Crum CP, Munger K. Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming. Proc Natl Acad Sci U S A. 2011;108:2130–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Melnick JL. Papova virus group. Science. 1962;135:1128–30.

    CAS  PubMed  Google Scholar 

  • Middleton K et al. Organization of human papillomavirus productive cycle during neoplastic progression provides a basis for selection of diagnostic markers. J Virol. 2003;77:10186–201.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moody CA, Laimins LA. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009;5:e1000605.

    PubMed Central  PubMed  Google Scholar 

  • Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer. 2010;10:550–60.

    CAS  PubMed  Google Scholar 

  • Moscicki AB, Ellenberg JH, Farhat S, Xu J. Persistence of human papillomavirus infection in HIV-infected and -uninfected adolescent girls: risk factors and differences, by phylogenetic type. J Infect Dis. 2004;190:37–45.

    PubMed  Google Scholar 

  • Muller M et al. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions. PLoS Pathog. 2012;8:e1002761.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Munger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J. 1989;8:4099–105.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Munoz N et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518–27.

    PubMed  Google Scholar 

  • Nakahara T, Nishimura A, Tanaka M, Ueno T, Ishimoto A, Sakai H. Modulation of the cell division cycle by human papillomavirus type 18 E4. J Virol. 2002;76:10914–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nayar R, Solomon D. Second edition of ‘The Bethesda System for reporting cervical cytology’ - atlas, website, and Bethesda interobserver reproducibility project. Cytojournal. 2004;1:4.

    PubMed Central  PubMed  Google Scholar 

  • Nelson LM, Rose RC, Moroianu J. Nuclear import strategies of high risk HPV16 L1 major capsid protein. J Biol Chem. 2002;277:23958–64.

    CAS  PubMed  Google Scholar 

  • Nicholls PK et al. Regression of canine oral papillomas is associated with infiltration of CD4+ and CD8+ lymphocytes. Virology. 2001;283:31–9.

    CAS  PubMed  Google Scholar 

  • Nomine Y et al. Domain substructure of HPV E6 oncoprotein: biophysical characterization of the E6 C-terminal DNA-binding domain. Biochemistry. 2003;42:4909–17.

    CAS  PubMed  Google Scholar 

  • Orth G. Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses. Ciba Found Symp. 1986;120:157–74.

    CAS  PubMed  Google Scholar 

  • Orth G, Favre M, Croissant O. Characterization of a new type of human papillomavirus that causes skin warts. J Virol. 1977;24:108–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Parish JL et al. E2 proteins from high- and low-risk human papillomavirus types differ in their ability to bind p53 and induce apoptotic cell death. J Virol. 2006;80:4580–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Patel D, Huang SM, Baglia LA, McCance DJ. The E6 protein of human papillomavirus type 16 binds to and inhibits co- activation by CBP and p300. EMBO J. 1999;18:5061–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pim D, Banks L. Interaction of viral oncoproteins with cellular target molecules: infection with high-risk vs low-risk human papillomaviruses. APMIS. 2010;118:471–93.

    CAS  PubMed  Google Scholar 

  • Poljak M, Cuzick J, Kocjan BJ, Iftner T, Dillner J, Arbyn M. Nucleic acid tests for the detection of alpha human papillomaviruses. Vaccine. 2012;30 Suppl 5:F100–6.

    CAS  PubMed  Google Scholar 

  • Rampias T et al. Activation of Wnt signaling pathway by human papillomavirus E6 and E7 oncogenes in HPV16-positive oropharyngeal squamous carcinoma cells. Mol Cancer Res. 2010;8: 433–43.

    CAS  PubMed  Google Scholar 

  • Rauber D, Mehlhorn G, Fasching PA, Beckmann MW, Ackermann S. Prognostic significance of the detection of human papilloma virus L1 protein in smears of mild to moderate cervical intraepithelial lesions. Eur J Obstet Gynecol Reprod Biol. 2008;140:258–62.

    CAS  PubMed  Google Scholar 

  • Reinson T et al. Engagement of the ATR-dependent DNA damage response at the human papillomavirus 18 replication centers during the initial amplification. J Virol. 2013;87:951–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Renoux VM et al. Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion. Eur J Immunol. 2011;41:3240–52.

    CAS  PubMed  Google Scholar 

  • Richards RM, Lowy DR, Schiller JT, Day PM. Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci U S A. 2006;103: 1522–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ristriani T et al. HPV oncoprotein E6 is a structure-dependent DNA-binding protein that recognizes four-way junctions. J Mol Biol. 2000;296:1189–203.

    CAS  PubMed  Google Scholar 

  • Ristriani T, Nomine Y, Masson M, Weiss E, Trave G. Specific recognition of four-way DNA junctions by the C-terminal zinc-binding domain of HPV oncoprotein E6. J Mol Biol. 2001;305: 729–39.

    CAS  PubMed  Google Scholar 

  • Romanczuk H, Thierry F, Howley PM. Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol. 1990;64:2849–59.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998;12: 2061–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Roperto S et al. PBMCs are additional sites of productive infection of bovine papillomavirus type 2. J Gen Virol. 2011;92:1787–94.

    CAS  PubMed  Google Scholar 

  • Sakakibara N, Mitra R, McBride AA. The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J Virol. 2011;85:8981–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schafer F, Florin L, Sapp M. DNA binding of L1 is required for human papillomavirus morphogenesis in vivo. Virology. 2002;295:172–81.

    PubMed  Google Scholar 

  • Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370:890–907.

    CAS  PubMed  Google Scholar 

  • Schiller JT, Castellsague X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine. 2012;30 Suppl 5:F123–38.

    CAS  PubMed  Google Scholar 

  • Schneider MA et al. The transcription factors TBX2 and TBX3 interact with human papillomavirus 16 (HPV16) L2 and repress the long control region of HPVs. J Virol. 2013;87:4461–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shai A, Brake T, Somoza C, Lambert PF. The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities. Cancer Res. 2007;67:1626–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shai A, Pitot HC, Lambert PF. E6-associated protein is required for human papillomavirus type 16 E6 to cause cervical cancer in mice. Cancer Res. 2010;70:5064–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shin MK, Sage J, Lambert PF. Inactivating all three rb family pocket proteins is insufficient to initiate cervical cancer. Cancer Res. 2012;72:5418–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sousa R, Dostatni N, Yaniv M. Control of papillomavirus gene expression. Biochim Biophys Acta. 1990;1032:19–37.

    CAS  PubMed  Google Scholar 

  • Spangle JM, Munger K. The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis. J Virol. 2010;84:9398–407.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spangle JM, Munger K. The HPV16 E6 oncoprotein causes prolonged receptor protein tyrosine kinase signaling and enhances internalization of phosphorylated receptor species. PLoS Pathog. 2013;9:e1003237.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Straight SW, Hinkle PM, Jewers RJ, McCance DJ. 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;67:4521–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Strauss MJ, Bunting H, Melnick JL. Virus-like particles and inclusion bodies in skin papillomas. J Invest Dermatol. 1950;15:433–44.

    CAS  PubMed  Google Scholar 

  • Swindle CS, Zou N, Van Tine BA, Shaw GM, Engler JA, Chow LT. Human papillomavirus DNA replication compartments in a transient DNA replication system. J Virol. 1999;73:1001–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tang S, Tao M, McCoy Jr JP, Zheng ZM. The E7 oncoprotein is translated from spliced E6*I transcripts in high-risk human papillomavirus type 16- or type 18-positive cervical cancer cell lines via translation reinitiation. J Virol. 2006;80:4249–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tao M, Kruhlak M, Xia S, Androphy E, Zheng ZM. Signals that dictate nuclear localization of human papillomavirus type 16 oncoprotein E6 in living cells. J Virol. 2003;77:13232–47.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thomas MC, Chiang CM. E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation. Mol Cell. 2005;17:251–64.

    CAS  PubMed  Google Scholar 

  • Todorovic B, Massimi P, Hung K, Shaw GS, Banks L, Mymryk JS. Systematic analysis of the amino acid residues of human papillomavirus type 16 E7 conserved region 3 involved in dimerization and transformation. J Virol. 2011;85:10048–57.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Todorovic B et al. Conserved region 3 of human papillomavirus 16 E7 contributes to deregulation of the retinoblastoma tumor suppressor. J Virol. 2012;86:13313–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trimble CL et al. Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium. J Immunol. 2010;185:7107–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  • van der Burg SH et al. Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens. Proc Natl Acad Sci U S A. 2007;104:12087–92.

    PubMed Central  PubMed  Google Scholar 

  • Veldman T, Horikawa I, Barrett JC, Schlegel R. Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16 E6 oncoprotein. J Virol. 2001;75:4467–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Veldman T, Liu X, Yuan H, Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci U S A. 2003;100:8211–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X et al. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA. 2009;15:637–47.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Meyers C, Wang HK, Chow LT, Zheng ZM. Construction of a full transcription map of human papillomavirus type 18 during productive viral infection. J Virol. 2011a;85:8080–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Meyers C, Guo M, Zheng ZM. Upregulation of p18Ink4c expression by oncogenic HPV E6 via p53-miR-34a pathway. Int J Cancer. 2011b;129:1362–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Helfer CM, Pancholi N, Bradner JE, You J. Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA. J Virol. 2013;87:3871–84.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X et al. miRNAs are biomarkers of oncogenic HPV infections. Proc Natl Acad Sci U S A. 2014;111(11):4262–7.

    CAS  PubMed  Google Scholar 

  • Weijzen S, Zlobin A, Braid M, Miele L, Kast WM. HPV16 E6 and E7 oncoproteins regulate Notch-1 expression and cooperate to induce transformation. J Cell Physiol. 2003;194:356–62.

    CAS  PubMed  Google Scholar 

  • Welters MJ et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res. 2008;14:178–87.

    CAS  PubMed  Google Scholar 

  • Wetherill LF et al. High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors. J Virol. 2012;86:5341–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  • White EA, Kramer RE, Tan MJ, Hayes SD, Harper JW, Howley PM. Comprehensive analysis of host cellular interactions with human papillomavirus E6 proteins identifies new E6 binding partners and reflects viral diversity. J Virol. 2012a;86:13174–86.

    CAS  PubMed Central  PubMed  Google Scholar 

  • White EA et al. Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses. Proc Natl Acad Sci U S A. 2012b;109:E260–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Woodham AW et al. The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection. PLoS One. 2012;7:e43519.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wright Jr TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. J Low Genit Tract Dis. 2007;11:223–39.

    PubMed  Google Scholar 

  • Xue Y et al. HPV16 E2 is an immediate early marker of viral infection, preceding E7 expression in precursor structures of cervical carcinoma. Cancer Res. 2010;70:5316–25.

    CAS  PubMed  Google Scholar 

  • You J, Croyle JL, Nishimura A, Ozato K, Howley PM. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell. 2004;117:349–60.

    CAS  PubMed  Google Scholar 

  • Zanier K et al. Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure. 2012;20:604–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zanier K et al. Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins. Science. 2013;339:694–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang B, Srirangam A, Potter DA, Roman A. HPV16 E5 protein disrupts the c-Cbl-EGFR interaction and EGFR ubiquitination in human foreskin keratinocytes. Oncogene. 2005;24:2585–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zheng ZM. Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses. Int J Biol Sci. 2010;6:730–55.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zheng ZM, Baker CC. Papillomavirus genome structure, expression, and post-transcriptional regulation. Front Biosci. 2006;11:2286–302.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zheng ZM, Wang X. Regulation of cellular miRNA expression by human papillomaviruses. Biochim Biophys Acta. 2011;1809:668–77.

    Google Scholar 

  • Zhou J, Sun XY, Louis K, Frazer IH. Interaction of human papillomavirus (HPV) type 16 capsid proteins with HPV DNA requires an intact L2 N-terminal sequence. J Virol. 1994;68:619–25.

    CAS  PubMed Central  PubMed  Google Scholar 

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  1. Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA

    Zhi-Ming Zheng

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  1. National Cancer Institute HIV/AIDS Malignancy Branch, National Institutes of Health, Bethesda, Maryland, USA

    Robert Yarchoan

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Zheng, ZM. (2014). Human Papillomaviruses. In: Yarchoan, R. (eds) Cancers in People with HIV and AIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0859-2_7

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