Skip to main content
SpringerLink
Log in
Book cover

Immunology, Phenotype First: How Mutations Have Established New Principles and Pathways in Immunology pp 59–83Cite as

Host Defenses Against Human Papillomaviruses: Lessons from Epidermodysplasia Verruciformis

  • Chapter

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 321))

Abstract

Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive genodermatosis associated with a high risk of skin carcinoma (MIM 226400). EV is characterized by the abnormal susceptibility of otherwise healthy patients to infection by specific, weakly virulent human papillomaviruses (HPVs), including the potentially oncogenic HPV-5. Inactivating mutations in either of the related EVER1/TMC6 and EVER2/TMC8 genes cause most EV cases. New insights in EV pathogenesis have been gained from the following recent observations: (1) EV-specific HPVs (betapapillomaviruses) are defective for an important growth-promoting function encoded by an E5/E8 gene present in other HPVs, and inactivation of EVER proteins may compensate for the missing viral function; (2) the transmembrane viral E5/E8 and cellular EVER proteins interact both with the zinc transporter ZnT1, and are likely to modulate zinc homeostasis. EV may thus represent a primary deficiency in intrinsic, constitutive immunity to betapapillomaviruses, or constitute a primary deficiency in innate immunity (or both). Keratinocytes, the home cells of HPVs, are likely to play a central role in both cases. An important issue is to establish which cellular genes involved in intrinsic and innate antiviral responses play a part in the outcome of infections with other HPV types, such as genital oncogenic HPVs.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

EV:

Epidermodysplasia verruciformis

HPV:

Human papillomavirus

PID:

Primary immunodeficiency disease

NMSC:

Nonmelanoma skin cancer

ORF:

Open reading frame

TGF-β:

Tumor growth factor beta

CMI:

Cell-mediated immunity

NK cell:

Natural killer cell

TNF-α:

Tumor necrosis factor alpha

SCID:

Severe combined immune deficiency

γc:

Common γc cytokine receptor subunit

JAK-3:

Janus kinase-3

WHIM syndrome:

Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome

SCC:

Squamous cell carcinoma

EGFR:

Epidermal growth factor receptor

CRPV:

Cottontail rabbit papillomavirus

ERK1/2:

Extracellular signal-regulated kinase 1/2

AP-1:

Activating protein-1

PCDH1:

Protocadherin 1

MTF1:

Metal-responsive element-binding transcription factor 1

cM:

Centimorgan

TMC:

Transmembrane channel-like

TLR:

Toll-like receptor

PAMP:

Pathogen-associated molecular pattern

References

  • Akgül B, Köse O, Safali M, Purdie K, Cerio R, Proby C, Storey A (2007) A distinct variant of epidermodysplasia verruciformis in a Turkish family lacking EVER1 and EVER2 mutations. J Dermatol Sci 46:214–216

    PubMed  Google Scholar 

  • Al-Gurairi FT, Al-Waiz M, Sharquie KE (2002) Oral zinc sulfate in the treatment of recalcitrant viral warts: randomized placebo-controlled clinical trial. Br J Dermatol 146:423–431

    PubMed  CAS  Google Scholar 

  • Alonso I, Fuchs E (2003) Stem cells of the skin epithelium. Proc Natl Acad Sci USA 100:11830–11835

    PubMed  CAS  Google Scholar 

  • Andrews GK, Wang H, Dey SK, Palmiter RD (2004) Mouse zinc transporter 1 gene provides an essential function during early embryonic development. Genesis 40:74–81

    PubMed  CAS  Google Scholar 

  • Androphy EJ, Dvoretzky I, Lowy DR (1985) X-linked inheritance of epidermodysplasia verruciformis: genetic and virologic studies of a kindred. Arch Dermatol 121:864–868

    PubMed  CAS  Google Scholar 

  • Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG (2000) The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. J Virol 74:11636–11641

    PubMed  CAS  Google Scholar 

  • Antonsson A, Karanfilovska S, Lindqvist PG, Hansson BG (2003) General acquisition of human papillomavirus infections of skin occurs in early infancy. J Clin Microbiol 4:2509–2514

    Google Scholar 

  • Archard HO, Heck JW, Stanley HR (1965) Focal epithelial hyperplasia: an unusual oral mucosal lesion found in Indian children. Oral Surg Oral Med Oral Pathol 20:201–212

    PubMed  CAS  Google Scholar 

  • Astori G, Lavergne D, Benton C, Hockmayr B, Egawa K, Garbe C, de Villiers EM (1998) Human papillomaviruses are commonly found in normal skin of immunocompetent hosts. J Invest Dermatol 110:752–755

    PubMed  CAS  Google Scholar 

  • Barr BB, Benton EC, Mc Laren K, Bunney MH, Smith IW, Blessing K, Hunter JA (1989) Human papillomavirus infection and skin cancer in renal allograft recipients. Lancet 1:124–129

    PubMed  CAS  Google Scholar 

  • Beaudenon S, Praetorius F, Kremsdorf D, Lutzner M, Worsaae N, Pehau-Arnaudet G, Orth G (1987) A new type of human papillomavirus associated with oral focal epithelial hyperplasia. J Invest Dermatol 88:130–135

    PubMed  CAS  Google Scholar 

  • Berthelot C, Dickerson MC, Rady P, He Q, Niroomand F, Tyring SK, Pandya AG (2007) Treatment of a patient with epidermodysplasia verruciformis carrying a novel EVER2 mutation with imiquimod. J Am Acad Dermatol 56:882–886

    PubMed  Google Scholar 

  • Beutler B, Jiang Z, Georgel P, Crozat K, Croker B, Rutschmann S, Du X, Hoebe K (2006) Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annu Rev Immunol 24:353–389

    PubMed  CAS  Google Scholar 

  • Bieniasz PD (2004) Intrinsic immunity: a front-line defense against viral attack. Nat Immunol 5:1109–1115

    PubMed  CAS  Google Scholar 

  • Blanpain C, Horsley V, Fuchs E (2007) Epithelial stem cells: turning over new leaves. Cell 128:445–458

    PubMed  CAS  Google Scholar 

  • Bos JD (ed) (2005) Skin immune system. Cutaneous immunology and clinical immunodermatology. 3rd edition, Boca Raton, CRC Press

    Google Scholar 

  • Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV (2002) The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55:244–265

    PubMed  CAS  Google Scholar 

  • Boxman ILA, Berkhout RJM, Mulder LHC, Wolkers MC, Bouwes Bavinck JN, Vermeer BJ, ter Schegget J (1997) Detection of human papillomavirus DNA in plucked hairs from renal transplant recipients and healthy volunteers. J Invest Dermatol 108:712–715

    PubMed  CAS  Google Scholar 

  • Brash DE (1997) Sunlight and the onset of skin cancer. Trends Genet 13:410–414

    PubMed  CAS  Google Scholar 

  • Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K (2002) Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell 2:567–578

    PubMed  CAS  Google Scholar 

  • Bruton OC (1952) Agammaglobulinemia. Pediatrics 9:722–728

    PubMed  CAS  Google Scholar 

  • Carré D, Dompmartin A, Verdon R, Comoz F, Le Brun E, Freymuth F, Leroy D (2003) Epidermodysplasia verruciformis in a patient with HIV infection: no response to highly active antiretroviral therapy. Int J Dermatol 42:296–300

    PubMed  Google Scholar 

  • Casanova JL, Abel L (2004) The human model: a genetic dissection of immunity to infection in natural conditions. Nat Rev Immunol 4:55–66

    PubMed  CAS  Google Scholar 

  • Casanova JL, Abel L (2007) Primary immunodeficiencies: a field in its infancy. Science 317:617–619

    PubMed  CAS  Google Scholar 

  • Casanova JL, Fieschi C, Bustamante J, Reichenbach J, Remus N, von Bernuth H, Picard C (2005) From idiopathic infectious diseases to novel primary immunodeficiencies. J Allergy Clin Immunol 116:426–430

    PubMed  CAS  Google Scholar 

  • Cockayne EA (1933) Inherited abnormalities of the skin and its appendages. Oxford University Press, London, p 156

    Google Scholar 

  • Coleman N, Birley HDL, Renton AM, Hanna NF, Ryait BK, Byrne M, Taylor-Robinson D, Stanley MA (1994) Immunological events in regressing genital warts. Am J Clin Pathol 102:768–774

    PubMed  CAS  Google Scholar 

  • Cooper KD, Androphy EJ, Lowy D, Katz SI (1990) Antigen presentation and T-cell activation in epidermodysplasia verruciformis. J Invest Dermatol 94:769–776

    PubMed  CAS  Google Scholar 

  • Cousins RJ, Liuzzi JP, Lichten LA (2006) Mammalian zinc transport, trafficking, and signals. J Biol Chem 281:24085–24089

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  • DiMaio D, Mattoon D (2001) Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene 20:7866–7873

    PubMed  CAS  Google Scholar 

  • Euvrard S, Kanitakis J, Claudy A (2003) Skin cancers after organ transplantation. N Engl J Med 345:1681–1691

    Google Scholar 

  • Fausch SC, Da Silva DM, Rudolf MP, Kast WM (2002) Human papillomavirus virus-like particles do not activate Langerhans cells: a possible immune escape mechanism used by human papillomaviruses. J Immunol 169:3242–3249

    PubMed  CAS  Google Scholar 

  • Favre M, Orth G, Majewski S, Baloul S, Pura A, Jablonska S (1998) Psoriasis: a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis. J Invest Dermatol 110:311–317

    PubMed  CAS  Google Scholar 

  • Favre M, Majewski S, Noszczyk B, Maienfisch F, Pura A, Orth G, Jablonska S (2000) Antibodies to human papillomavirus type 5 are generated in epidermal repair processes. J Invest Dermatol 114:403–407

    PubMed  CAS  Google Scholar 

  • Feltkamp MCW, Broer R, di Summa FM, Struijk L, van der Meijden E, Verlaan BPJ, Westendorp RGJ, ter Schegget J, Spaan WJM, Bouwes Bavinck JN (2003) Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Cancer Res 63:2695–2700

    PubMed  CAS  Google Scholar 

  • Fischer A (2004) Human primary immunodeficiency diseases: a perspective. Nat Immunol 5:23–30

    PubMed  CAS  Google Scholar 

  • Fischer WC, Black RE (2004) Zinc and the risk for infectious disease. Annu Rev Nutr 24:255–275

    Google Scholar 

  • Frank M, Kemler R (2002) Protocadherins. Curr Opin Cell Biol 14:557–562

    PubMed  CAS  Google Scholar 

  • Frazer IH, Thomas R, Zhou J, Leggatt GR, Dunn L, McMillan N, Tindle RW, Filgueira L, Manders P, Barnard P, Sharkey M (1999) Potential strategies utilised by papillomavirus to evade host immunity. Immunol Rev 168:131–142

    PubMed  CAS  Google Scholar 

  • Friedewald WF (1944) Certain conditions determining enhanced infection with the rabbit papilloma virus. J Exp Med 80:65–76

    PubMed  CAS  Google Scholar 

  • Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778

    PubMed  CAS  Google Scholar 

  • Fuchs PG, Pfister H (1996) Papillomaviruses in epidermodysplasia verruciformis. In: Lacey C (ed) Papillomavirus reviews: current research on papillomaviruses, vol 2 (The papillomaviruses). Leeds University Press, Leeds, pp 253–261

    Google Scholar 

  • Garcia-Vallvé S, Alonso A, Bravo IG (2005) Papillomaviruses: different genes have different histories. Trends Microbiol 13:514–521

    PubMed  Google Scholar 

  • Genther Williams SM, Disbrow GL, Schlegel R, Lee D, Threadgill DW, Lambert PF (2005) Requirement of epidermal growth factor receptor for hyperplasia induced by E5, a high-risk human papillomavirus oncogene. Cancer Res 65:6534–6542

    PubMed  CAS  Google Scholar 

  • Glinski W, Jablonska S, Langner A, Obalek S, Haftek M, Proniewska M (1976) Cell-mediated immunity in epidermodysplasia verruciformis. Dermatologica 153:218–227

    PubMed  CAS  Google Scholar 

  • Glinski W, Obalek S, Jablonska S, Orth G (1981) T-cells defect in patients with epidermodysplasia verruciformis due to human papillomavirus types 3 and 5. Dermatologica 162:141–147

    PubMed  CAS  Google Scholar 

  • Gober MD, Rady PL, He Q, Turker SB, Tyring SK, Gaspari AA (2007) Novel homozygous frameshift mutation of EVER1 gene in an epidermodysplasia verruciformis patient. J Invest Dermatol 127:817–820

    PubMed  CAS  Google Scholar 

  • Gorlin RJ, Gelb B, Diaz GA, Lofsness KG, Pittelkow MR, Fenyk JR (2000) WHIM syndrome, an autosomal dominant disorder: clinical, hematological, and molecular studies. Am J Med Genet 91:368–376

    PubMed  CAS  Google Scholar 

  • Guess JC, McCance DJ (2005) Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3a production. J Virol 79:14852–14862

    PubMed  CAS  Google Scholar 

  • Harry JB, Wettstein FO (1996) Transforming properties of the cottontail rabbit papillomavirus oncoproteins LE6 and SE6 and the E8 protein. J Virol 70:3355–3362

    PubMed  CAS  Google Scholar 

  • Harwood CA, Proby CM (2002) Human papillomaviruses and non-melanoma skin cancer. Curr Opin Infect Dis 15:101–114

    PubMed  Google Scholar 

  • Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, Klotman ME, Diaz GA (2003) Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet 34:70–74

    PubMed  CAS  Google Scholar 

  • Howley PM, Lowy DR (2007) Papillomaviruses. In: Knipe DM, Howley PM, Griffin DE, et al (eds) Fields virology, 5th edn. Wolters Kluwer/Lippincott Williams and Wilkins, Philadelphia, pp 2299–2354

    Google Scholar 

  • Hu J, Han R, Cladel NM, Pickel MD, Christensen ND (2002) Intracutaneous DNA vaccination with the E8 gene of cottontail rabbit papillomavirus induces protective immunity against virus challenge in rabbits. J Virol 76:6453–6459

    PubMed  CAS  Google Scholar 

  • Jablonska S, Formas I (1959) Weitere positive Ergebnisse mit Auto- und Heteroinokulation bei Epidermodysplasia verruciformis Lewandowsky-Lutz. Dermatologica 118:86–93

    Google Scholar 

  • Jablonska S, Orth G (1985) Epidermodysplasia verruciformis. Clin Dermatol 3(4):83–96

    PubMed  CAS  Google Scholar 

  • Jablonska S, Dabrowski J, Jakubowicz K (1972) Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Res 32:583–589

    PubMed  CAS  Google Scholar 

  • Jablonska S, Orth G, Jarzabek-Chorzelska M, Rzesa G, Obalek S, Glinski W, Favre M, Croissant O (1979) Epidermodysplasia verruciformis versus disseminated verrucae planae: is epidermodysplasia verruciformis a generalized infection with wart virus? J Invest Dermatol 72: 114–119

    PubMed  CAS  Google Scholar 

  • Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A, Green AC, Bouwes Bavinck JN, Perry A, Spencer S, Rees JR, Mott LA, Pawlita M (2006) Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 98:389–395

    Article  PubMed  Google Scholar 

  • Kawai T, Akira S (2006) Innate immune recognition of viral infection. Nat Immunol 7:131–137

    PubMed  CAS  Google Scholar 

  • Kawashima M, Favre M, Obalek S, Jablonska S, Orth G (1990) Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses. J Invest Dermatol 95:537–542

    PubMed  CAS  Google Scholar 

  • Keresztes G, Mutai H, Heller S (2003) TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins. BMC Genomics 4:24–35

    PubMed  Google Scholar 

  • Khattar JA, Musharrafieh UM, Tamim H, Hamadeh GN (2007) Topical zinc oxide vs. salicylic acid-lactic acid combination in the treatment of warts. Int J Dermatol 46:427–430

    PubMed  CAS  Google Scholar 

  • Kitamura H, Morikawa H, Kamon H, Iguchi M, Hojyo S, Fukada T, Yamashita S, Kaisho T, Akira S, Murakami M, Hirano T (2006) Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol 7:971–977

    PubMed  CAS  Google Scholar 

  • Koranda FC, Dehmel EM, Kahn G, Penn I (1974) Cutaneous complications in immunosuppressed renal homograft recipients. J Am Med Assoc 229:419–424

    CAS  Google Scholar 

  • Koromilas AE, Li S, Matlashewski G (2001) Control of interferon signaling in human papillomavirus infection. Cytokine Growth Factor Rev 12:157–170

    PubMed  CAS  Google Scholar 

  • Kröncke KD (2007) Cellular stress and intracellular zinc dyshomeostasis. Arch Biochem Biophys 463:183–187

    PubMed  Google Scholar 

  • Kupper TS, Fuhlbrigge RC (2004) Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 4:211–212

    PubMed  CAS  Google Scholar 

  • Kurima K, Peters LM, Yang Y, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo J, Makishima T, Ghosh M, Menon PSN, Deshmukh D, Oddoux C, Ostrer H, Khan S, Riazuddin S, Deininger PL, Hampton LL, Sullivan SL, Battey JF, Keats BJB, Wilcox ER, Friedman TB, Griffith AJ (2002) Dominant and recessive deafness caused by mutations of a novel gene TMC1 required for cochlear hair-cell function. Nat Genet 30:277–284

    PubMed  Google Scholar 

  • Kurima K, Yang Y, Sorber K, Griffith AJ (2003) Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis. Genomics 82:300–308

    PubMed  CAS  Google Scholar 

  • Laffort C, Le Deist F, Favre M, Caillat-Zucman S, Radford-Weiss I, Debré M, Fraitag S, Blanche S, Cavazzana-Calvo M, de Saint Basile G, de Villartay P, Giliani S, Orth G, Casanova JL, Bodemer C, Fischer A (2004) Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gamma cytokine receptor subunit or JAK-3 deficiency. Lancet 363:2051–2054

    PubMed  CAS  Google Scholar 

  • Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M (2008) Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. J Exp Med 205:35–42

    PubMed  CAS  Google Scholar 

  • Lebre MC, van der Aar AM, van Baarsen L, van Capel TMM, Schuitemaker JHN, Kapsenberg ML, de Jong EC (2007) Human keratinocytes express functional Toll-like receptor 3, 4, 5 and 9. J Invest Dermatol 127:331–341

    PubMed  CAS  Google Scholar 

  • Lewandowsky F, Lutz W (1922) Ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis). AMA Arch Derm Syphilol 141:193–203

    Google Scholar 

  • Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci USA 102:6843–6848

    PubMed  CAS  Google Scholar 

  • Longworth MS, Laimins LA (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68:362–372

    PubMed  CAS  Google Scholar 

  • Lutz WA (1946) A propos de l’épidermodysplasie verruciforme. Dermatologica 92:30–43

    Google Scholar 

  • Lutzner MA (1978) Epidermodysplasia verruciformis: an autosomal recessive disease characterized by viral warts and skin cancer. A model for viral oncogenesis. Bull Cancer 65:169–182

    PubMed  CAS  Google Scholar 

  • Lutzner MA, Croissant O, Ducasse MF, Kreis H, Crosnier J, Orth G (1980) A potentially oncogenic human papillomavirus (HPV5) found in two renal allograft recipients. J Invest Dermatol 75:353–356

    PubMed  CAS  Google Scholar 

  • Lutzner MA, Orth G, Dutronquay V, Ducasse MF, Kreis H, Crosnier J (1983) Detection of human papillomavirus type 5 DNA in skin cancers of an immunosuppressed renal allograft recipient. Lancet 2:422–424

    PubMed  CAS  Google Scholar 

  • Lutzner MA, Blanchet-Bardon C, Orth G (1984) Clinical observations, virologic studies, and treatment trials in patients with epidermodysplasia verruciformis, a disease induced by specific human papillomaviruses. J Invest Dermatol 83:18s–25s

    PubMed  CAS  Google Scholar 

  • Majewski S, Jablonska S (1992) Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancers: the role of local immunosurveillance. Am J Med Sci 304:174–179

    PubMed  CAS  Google Scholar 

  • Majewski S, Jablonska S (1995) Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin. Arch Dermatol 131:1312–1318

    PubMed  CAS  Google Scholar 

  • Majewski S, Skopinska-Rozewska E, Jablonska S, Wasik M, Misiewicz J, Orth G (1986) Partial defects of cell mediated immunity in patients with epidermodysplasia verruciformis. J Am Acad Dermatol 15:966–973

    PubMed  CAS  Google Scholar 

  • Majewski S, Malejczyk J, Jablonska S, Misiewicz J, Rudnicka L, Obalek S, Orth G (1990) Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis. J Am Acad Dermatol 22:423–427

    PubMed  CAS  Google Scholar 

  • Majewski S, Hunzelmann N, Nischt R, Eckes B, Rudnicka L, Orth G (1991) TGF beta-1 and TNF alpha expression in the epidermis of patients with epidermodysplasia verruciformis. J Invest Dermatol 97:862–867

    PubMed  CAS  Google Scholar 

  • Majewski S, Jablonska S, Orth G (1997) Epidermodysplasia verruciformis. Immunological and nonimmunological surveillance mechanisms: role in tumor progression. Clin Dermatol 15:321–334

    PubMed  CAS  Google Scholar 

  • Majewski S, Jablonska S, Favre M, Ramoz N, Orth G (1999) Papillomavirus and autoimmunity in psoriasis. Immunol Today 20:475–476

    PubMed  CAS  Google Scholar 

  • Marcotti W, Erven A, Johnson SL, Steel KP, Kros CJ (2006) Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea. J Physiol 574:677–698

    PubMed  CAS  Google Scholar 

  • Maufort JP, Williams SM, Pitot HC, Lambert PF (2007) Human papillomavirus 16 E5 oncogene contributes to two stages of skin carcinogenesis. Cancer Res 67:6106–6112

    PubMed  CAS  Google Scholar 

  • Mendoza JA, Jacob Y, Cassonnet P, Favre M (2006) Human papillomavirus type 5 E6 oncoprotein represses the transforming growth factor b signaling pathway by binding to SMAD3. J Virol 80:12420–12424

    PubMed  CAS  Google Scholar 

  • Miller LS, Modlin RL (2007) Human keratinocyte Toll-like receptors promote distinct immune responses. J Invest Dermatol 127:262–263

    PubMed  CAS  Google Scholar 

  • Münger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, Grace M, Huh KW (2004) Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78:11451–11460

    PubMed  Google Scholar 

  • Nickoloff BJ (2007) Cracking the cytokine code in psoriasis. Nat Med 13:242–244

    PubMed  CAS  Google Scholar 

  • Nonnenmacher M, Salmon J, Jacob Y, Orth G, Breitburd F (2006) Cottontail rabbit papillomavirus E8 protein is essential for wart formation and provides new insights into viral pathogenesis. J Virol 80:4890–4900

    PubMed  CAS  Google Scholar 

  • Obalek S, Favre M, Szymanczyk J, Misiewicz J, Jablonska S, Orth G (1992) Human papillomavirus (HPV) types specific of epidermodysplasia verruciformis detected in warts induced by HPV3 or HPV3-related types in immunosuppressed patients. J Invest Dermatol 98:936–941

    PubMed  CAS  Google Scholar 

  • Oliveira WRP, Carrasco S, Neto CF, Rady P, Tyring SK (2003) Nonspecific cell-mediated immunity in patients with epidermodysplasia verruciformis. J Dermatol 30:203–209

    Google Scholar 

  • Orth G (1987) Epidermodysplasia verruciformis. In: Howley PM, Salzman NP (eds) The papovaviridae. Vol 2 The papillomaviruses. Plenum Publishing, New York, pp 199–243

    Google Scholar 

  • Orth G (2004) Human papillomaviruses and the skin: more to be learned. J Invest Dermatol 123:xi–xiii

    PubMed  CAS  Google Scholar 

  • Orth G (2005) Human papillomaviruses associated with epidermodysplasia verruciformis in non-melanoma skin cancers: guilty or innocent? J Invest Dermatol 125:xii–xiii

    PubMed  CAS  Google Scholar 

  • Orth G (2006) Genetics of epidermodysplasia verruciformis: insights into host defense against papillomaviruses. Semin Immunol 18:362–374

    PubMed  CAS  Google Scholar 

  • Orth G (2008) General features of human papillomaviruses. In: Mahy B, Van Regelmortel M (eds) Encyclopedia of virology, 3rd edn. Elsevier, Oxford (in press)

    Google Scholar 

  • Orth G, Jablonska S, Favre M, Croissant O, Jarzabek-Chorzelska M, Rzesa G (1978) Characterization of two types of human papillomaviruses in lesions of epidermodysplasia verruciformis. Proc Natl Acad Sci USA 75:1537–1541

    PubMed  CAS  Google Scholar 

  • Orth G, Jablonska S, Jarzabek-Chorzelska M, Rzesa G, Obalek S, Favre M, Croissant O (1979) Characteristics of the lesions and risk of malignant conversion as related to the type of the human papillomavirus involved in epidermodysplasia verruciformis. Cancer Res 39:1074–1082

    PubMed  CAS  Google Scholar 

  • Orth G, Favre M, Breitburd F, Croissant O, Jablonska S, Obalek S, Jarzabek-Chorzelska M, Rzesa G (1980) Epidermodysplasia verruciformis: a model for the role of papillomaviruses in human cancer. Cold Spring Harbor Conf Cell Prolif 7:259–282

    CAS  Google Scholar 

  • Orth G, Favre M, Majewski S, Jablonska S (2001) Epidermodysplasia verruciformis defines a subset of cutaneous human papillomaviruses. J Virol 75:4952–4953

    PubMed  CAS  Google Scholar 

  • Ostrow RS, Bender M, Niimura M, Seki T, Kawashima M, Pass F, Faras AJ (1982) Human papillomavirus DNA in cutaneous primary and metastasized squamous cell carcinomas from patients with epidermodysplasia verruciformis. Proc Natl Acad Sci USA 79:1634–1638

    PubMed  CAS  Google Scholar 

  • Palmiter RD, Findley SD (1995) Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14:639–649

    PubMed  CAS  Google Scholar 

  • Pass F, Reissig M, Shah KV, Eisinger M, Orth G (1977) Identification of an immunologically distinct papillomavirus from lesions of epidermodysplasia verruciformis. J Natl Cancer Inst 59:1107–1112

    PubMed  CAS  Google Scholar 

  • Pfister H (2003) Human papillomavirus and skin cancer. J Natl Cancer Inst Monogr 31:52–56

    PubMed  Google Scholar 

  • Pfister H, Gassenmaier A, Nürnberger F, Stüttgen G (1983) Human papillomavirus 5-DNA in carcinoma of an epidermodysplasia verruciformis patient infected with various human papillomavirus types. Cancer Res 43:1436–1441

    PubMed  CAS  Google Scholar 

  • Prawer SE, Pass F, Vance JC, Greenberg LJ, Yunis EJ, Zelickson AS (1977) Depressed immune function in epidermodysplasia verruciformis. Arch Dermatol 113:495–499

    PubMed  CAS  Google Scholar 

  • Ramoz N, Rueda LA, Bouadjar B, Favre M, Orth G (1999) A susceptibility locus for epidermodysplasia verruciformis, an abnormal predisposition to infection with the oncogenic human papillomavirus type 5, maps to chromosome 17qter in a region containing a psoriasis locus. J Invest Dermatol 112:259–263

    PubMed  CAS  Google Scholar 

  • Ramoz N, Taieb A, Rueda LA, Montoya LS, Bouadjar B, Favre M, Orth G (2000) Evidence for a nonallelic heterogeneity of epidermodysplasia verruciformis with two susceptibility loci mapped to chromosome regions 2p21–p24 and 17q 25. J Invest Dermatol 114:1148–1153

    PubMed  CAS  Google Scholar 

  • Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M (2002) Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet 32:579–581

    PubMed  CAS  Google Scholar 

  • Rink L, Haase H (2007) Zinc homeostasis and immunity. Trends Immunol 28:1–4

    PubMed  CAS  Google Scholar 

  • Schiffman M, Kjaer SK (2003) Natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr 31:14–19

    PubMed  Google Scholar 

  • Spahl DU, Berendji-Grün D, Suschek CV, Kolb-Bachofen V, Kröncke KD (2003) Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release. Proc Natl Acad Sci USA 100:13952–13957

    PubMed  CAS  Google Scholar 

  • Stanley M (2006) Immune responses to human papillomavirus. Vaccine 24 [Suppl 1]:S16–S22

    PubMed  Google Scholar 

  • Stark S, Petridis AK, Ghim S, Jenson AB, Bavinck JNB, Gross G, Stockfleth E, Fuchs PG, Pfister H (1998) Prevalence of antibodies against virus-like particles of epidermodysplasia verruciformis-associated HPV8 in patients at risk of skin cancer. J Invest Dermatol 111:696–701

    PubMed  CAS  Google Scholar 

  • Storey A (2002) Papillomaviruses: death-defying acts in skin cancer. Mol Med 8:417–421

    CAS  Google Scholar 

  • Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 101:6062–6067

    PubMed  CAS  Google Scholar 

  • Sun XK, Chen JF, Xu AE (2005) A homozygous nonsense mutation in the EVER2 gene leads to epidermodysplasia verruciformis. Clin Exp Dermatol 30:573–574

    PubMed  Google Scholar 

  • Tagami H, Aiba S, Rokugo M (1985) Regression of flat warts and common warts. Clin Dermatol 3(4):170–178

    PubMed  CAS  Google Scholar 

  • Tate G, Suzuki T, Kishimoto K, Mitsuya T (2004) Novel mutations of EVER1/TMC6 gene in a Japanese patient with epidermodysplasia verruciformis. J Hum Genet 49:223–225

    PubMed  CAS  Google Scholar 

  • Ullrich SE (2005) Mechanisms underlying UV-induced immune suppression. Mutat Res 571:185–205

    PubMed  CAS  Google Scholar 

  • von Bülow V, Rink L, Haase H (2005) Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression suppresses TNF-alpha and IL-1beta production in monocytes by elevation of guanosine 3c, 5,-cyclic monophosphate1. J Immunol 175:4697–4705

    Google Scholar 

  • Vreugde S, Erven A, Kros CJ, Marcotti W, Fuchs H, Kurima K, Wilcox ER, Friedman TB, Griffith AJ, Balling R, Hrabé de Angelis MH, Avraham KB, Steel KP (2002) Beethoven, a mouse model for dominant, progressive hearing loss DFNA36. Nat Genet 30:257–258

    PubMed  Google Scholar 

  • Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J (2002) A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet 71:66–73

    PubMed  CAS  Google Scholar 

  • Weissenborn SJ, Höptl R, Weber F, Smola H, Pfister HJ, Fuchs PG (1999) High prevalence of a variety of epidermodysplasia verruciformis-associated human papillomaviruses in psoriasis skin of patients treated or not treated with PUVA. J Invest Dermatol 113:122–126

    PubMed  CAS  Google Scholar 

  • Wellinghausen N, Kirchner H, Rink L (1997) The immunobiology of zinc. Immunol Today 18:519–521

    PubMed  CAS  Google Scholar 

  • Woodworth CD (2002) HPV innate immunity. Front Biosci 7:2058–2071

    Google Scholar 

  • Yamasaki S, Sakata-Sogawa K, Hasegawa A, Suzuki T, Kabu K, Sato E, Kurosaki T, Yamashita S, Tokunaga M, Nishida K, Hirano T (2007) Zinc is a novel intracellular second messenger. J Cell Biol 177:637–645

    PubMed  CAS  Google Scholar 

  • Yamashita S, Miyagi C, Fukada T, Kagara N, Che YS, Hirano T (2004) Zinc transporter LIV1 controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature 429:298–302

    PubMed  CAS  Google Scholar 

  • Yang R, Murillo FM, Cui H, Blosser R, Uematsu S, Takeda K, Akira S, Viscidi RP, Roden RB (2004) Papillomavirus-like particles stimulate murine bone marrow-derived dendritic cells to produce alpha interferon and Th1 immune responses via MyD88. J Virol 78:11152–11160

    PubMed  CAS  Google Scholar 

  • Yang R, Murillo FM, Delannoy MJ, Blosser LR, Yutzy WH, Uematsu S, Takeda K, Akira S, Viscidi R, Roden RB (2005) B lymphocyte activation by human papillomavirus-like particles directly induces Ig class switch recombination via TLR4-MyD88. J Immunol 174:7912–7929

    PubMed  CAS  Google Scholar 

  • Zhou Z, Wang L, Song Z, Saari JT, McClain CJ, Kang YJ (2004) Abrogation of nuclear factor-κB activation is involved in zinc inhibition of lipopolysaccharide-induced tumor necrosis factor-a production and liver injury. Am J Pathol 164:1547–1556

    PubMed  CAS  Google Scholar 

  • Zuo YG, Ma D, Zhang Y, Qiao J, Wang B (2006) Identification of a novel mutation and a genetic polymorphism of EVER1 gene in two families with epidermodysplasia verruciformis. J Dermatol Sci 44:153–159

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Virology, Institut Pasteur, 25 Rue du Docteur Roux, 75015, Paris, France

    G. Orth

Authors
  1. G. Orth
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Immunology, Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037, USA

    Bruce Beutler

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Orth, G. (2008). Host Defenses Against Human Papillomaviruses: Lessons from Epidermodysplasia Verruciformis. In: Beutler, B. (eds) Immunology, Phenotype First: How Mutations Have Established New Principles and Pathways in Immunology. Current Topics in Microbiology and Immunology, vol 321. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75203-5_3

Download citation

Publish with us

Policies and ethics

Search

Navigation