DOI: 10.1099/vir.0.83317-0. Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes

Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes

10.1099/vir.0.83317-0

Crossref journal-article

Microbiology Society

Journal of General Virology (345)

Abstract

Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC). The role of betapapillomaviruses in the development of cutaneous SCC is, however, still enigmatic. The ability to inhibit UVB-induced apoptosis, as demonstrated for HPV5 in vitro, may be important in this respect, as survival of DNA-damaged and mutated cells increases the risk of transformation. The aim of this study was to assess whether inhibition of UVB-induced apoptosis is a general property of betapapillomaviruses and to identify apoptotic factors that are potentially involved in this process. Primary human keratinocytes transduced with E6 and E7 of selected betapapillomaviruses (HPV5, HPV8, HPV15, HPV20, HPV24 and HPV38) were characterized and subjected to UVB irradiation. HPV8- and HPV20-expressing keratinocytes in particular showed fewer signs of apoptosis, as demonstrated by lower levels of active caspase 3, less enzymic caspase activity and less DNA fragmentation. The observed inhibition of UVB-induced apoptosis was mediated by E6 and coincided with reduced steady-state expression of the pro-apoptotic protein Bax. In conclusion, E6 of HPV8 and HPV20 reduces the apoptotic responses upon UVB irradiation when expressed in primary human keratinocytes. Infections with HPV8 and HPV20 may therefore augment the carcinogenic effect of UV radiation and potentially contribute to oncogenic transformation of the skin.

Bibliography

Struijk, L., van der Meijden, E., Kazem, S., ter Schegget, J., de Gruijl, F. R., Steenbergen, R. D. M., & Feltkamp, M. C. W. (2008). Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes. Journal of General Virology, 89(9), 2303â2314.

Authors 7

Linda Struijk (first)
Els van der Meijden (additional)
Siamaque Kazem (additional)
Jan ter Schegget (additional)
Frank R. de Gruijl (additional)
Renske D. M. Steenbergen (additional)
Mariet C. W. Feltkamp (additional)

References 43 Referenced 54

10.1038/sj.embor.7400615 / EMBO Rep / Skin human papillomavirus type 38 alters p53 functions by accumulation of ΔNp73 by Accardi (2006)
10.1006/viro.1999.9675 / Virology / HPV16 E6 oncoprotein inhibits apoptosis induced during serum-calcium differentiation of foreskin human keratinocytes by Alfandari (1999)
10.1056/NEJMp048086 / N Engl J Med / Milk of human kindness? – HAMLET, human papillomavirus, and warts by Bouwes Bavinck (2004)
10.1002/(SICI)1097-0215(20000401)86:1<118::AID-IJC18>3.0.CO;2-2 / The Nambour Skin Cancer Prevention Study Group. Int J Cancer / Case–control study in a subtropical Australian population to assess the relation between non-melanoma skin cancer and epidermodysplasia verruciformis human papillomavirus DNA in plucked eyebrow hairs by Boxman (2000)
10.1046/j.1523-1747.2001.01499.x / J Invest Dermatol / Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses by Boxman (2001)
10.1038/sj.onc.1203375 / Oncogene / Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein by Caldeira (2000)
10.1128/JVI.77.3.2195-2206.2003 / J Virol / The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties by Caldeira (2003)
10.1111/j.0906-6705.2005.00384.x / Exp Dermatol / Apoptosis induced by ultraviolet B in HPV-immortalized human keratinocytes requires caspase-9 and is death receptor independent by Daher (2006)
10.1128/JCM.44.5.1792-1800.2006 / J Clin Microbiol / Evaluation of a novel highly sensitive, broad-spectrum PCR-reverse hybridization assay for detection and identification of beta-papillomavirus DNA by de Koning (2006)
10.1099/vir.0.82732-0 / J Gen Virol / Betapapillomaviruses frequently persist in the skin of healthy individuals by de Koning (2007)
10.1016/j.virol.2004.03.033 / Virology / Classification of papillomaviruses by de Villiers (2004)
10.1128/JVI.79.23.14899-14908.2005 / J Virol / Skin hyperproliferation and susceptibility to chemical carcinogenesis in transgenic mice expressing E6 and E7 of human papillomavirus type 38 by Dong (2005)
{'key': 'R13', 'first-page': '2695', 'article-title': 'Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer', 'volume': '63', 'author': 'Feltkamp', 'year': '2003', 'journal-title': 'Cancer Res'} / Cancer Res / Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer by Feltkamp (2003)
10.1074/jbc.M200113200 / J Biol Chem / The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis by Filippova (2002)
10.1074/jbc.M401172200 / J Biol Chem / The human papillomavirus 16 E6 protein binds to Fas-associated death domain and protects cells from Fas-triggered apoptosis by Filippova (2004)
10.1038/sj.bjc.6601829 / Br J Cancer / Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomavirus types 5 and 18 by Giampieri (2004)
10.1002/ijc.22591 / Int J Cancer / Selective induction of apoptosis by leptomycin B in keratinocytes expressing oncogenes by Gray (2007)
10.1097/00001432-200204000-00002 / Curr Opin Infect Dis / Human papillomaviruses and non-melanoma skin cancer by Harwood (2002)
10.1046/j.1523-1747.1998.00240.x / J Invest Dermatol / Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers by Harwood (1998)
10.1002/1096-9071(200007)61:3<289::AID-JMV2>3.0.CO;2-Z / J Med Virol / Human papillomavirus infection and non-melanoma skin cancer in immunosuppressed and immunocompetent individuals by Harwood (2000)
10.1093/emboj/cdf443 / EMBO J / Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1 by Iftner (2002)
10.1038/sj.onc.1203339 / Oncogene / E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage by Jackson (2000)
10.1101/gad.182100 / Genes Dev / Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins by Jackson (2000)
10.1093/jnci/djj092 / J Natl Cancer Inst / Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin by Karagas (2006)
10.1007/s10495-006-0004-1 / Apoptosis / Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria by Leverrier (2007)
10.1099/vir.0.80453-0 / J Gen Virol / Downregulation of Bax mRNA expression and protein stability by the E6 protein of human papillomavirus 16 by Magal (2005)
{'key': 'R27', 'first-page': '323', 'article-title': 'Cellular transformation by papillomavirus oncoproteins', 'volume': '1155', 'author': 'Mansur', 'year': '1993', 'journal-title': 'Biochim Biophys Acta'} / Biochim Biophys Acta / Cellular transformation by papillomavirus oncoproteins by Mansur (1993)
10.1001/archderm.139.7.890 / Arch Dermatol / Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals by Masini (2003)
10.1128/JVI.00954-06 / J Virol / E6/E7 expression of human papillomavirus type 20 (HPV-20) and HPV-27 influences proliferation and differentiation of the skin in UV-irradiated SKH-hr1 transgenic mice by Michel (2006)
10.1111/j.0906-6705.2005.00296.x / Exp Dermatol / E6* oncoprotein expression of human papillomavirus type-16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defence by Mouret (2005)
10.1111/j.1349-7006.1991.tb01802.x / Jpn J Cancer Res / Tumorigenic transformation of primary rat embryonal fibroblasts by human papillomavirus type 8 E7 gene in collaboration with the activated H-ras gene by Nishikawa (1991)
10.1373/49.3.425 / Clin Chem / PCR-based calibration curves for studies of quantitative gene expression in human monocytes: development and evaluation by Ovstebo (2003)
10.1007/s00403-003-0435-2 / Arch Dermatol Res / High prevalence of epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population by Pfister (2003)
10.1158/0008-5472.CAN-04-3263 / Cancer Res / Development of skin tumors in mice transgenic for early genes of human papillomavirus type 8 by Schaper (2005)
10.1128/JVI.68.11.7051-7059.1994 / J Virol / 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 by Schmitt (1994)
10.1074/jbc.M200281200 / J Biol Chem / HPV-16 E6/7 immortalization sensitizes human keratinocytes to ultraviolet B by altering the pathway from caspase-8 to caspase-9-dependent apoptosis by Simbulan-Rosenthal (2002)
10.1016/j.jcv.2004.11.019 / J Clin Virol / HPV-mediated transformation of the anogenital tract by Steenbergen (2005)
10.1046/j.1523-1747.2003.12632.x / J Invest Dermatol / Presence of human papillomavirus DNA in plucked eyebrow hairs is associated with a history of cutaneous squamous cell carcinoma by Struijk (2003)
10.1038/sj.onc.1202223 / Oncogene / Inhibition of Bak-induced apoptosis by HPV-18 E6 by Thomas (1998)
10.1099/0022-1317-80-6-1513 / J Gen Virol / Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types by Thomas (1999)
10.1038/sj.onc.1209429 / Oncogene / Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein by Vogt (2006)
{'key': 'R42', 'first-page': '2433', 'article-title': 'Biological and biochemical activity of E7 genes of the cutaneous human papillomavirus type 5 and 8', 'volume': '8', 'author': 'Yamashita', 'year': '1993', 'journal-title': 'Oncogene'} / Oncogene / Biological and biochemical activity of E7 genes of the cutaneous human papillomavirus type 5 and 8 by Yamashita (1993)
10.1038/nrc798 / Nat Rev Cancer / Papillomaviruses and cancer: from basic studies to clinical application by zur Hausen (2002)

Dates

Type	When
Created	17 years ago (Aug. 27, 2008, 11:45 a.m.)
Deposited	4 years, 9 months ago (Nov. 4, 2020, 7:42 a.m.)
Indexed	4 months, 3 weeks ago (April 6, 2025, 6:03 p.m.)
Issued	16 years, 11 months ago (Sept. 1, 2008)
Published	16 years, 11 months ago (Sept. 1, 2008)
Published Print	16 years, 11 months ago (Sept. 1, 2008)

Funders 0

None

BibTeX

@article{Struijk_2008, title={Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes}, volume={89}, ISSN={1465-2099}, url={http://dx.doi.org/10.1099/vir.0.83317-0}, DOI={10.1099/vir.0.83317-0}, number={9}, journal={Journal of General Virology}, publisher={Microbiology Society}, author={Struijk, Linda and van der Meijden, Els and Kazem, Siamaque and ter Schegget, Jan and de Gruijl, Frank R. and Steenbergen, Renske D. M. and Feltkamp, Mariet C. W.}, year={2008}, month=sep, pages={2303–2314} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        4,
        6
      ]
    ],
    "date-time": "2025-04-06T22:03:20Z",
    "timestamp": 1743977000870
  },
  "reference-count": 43,
  "publisher": "Microbiology Society",
  "issue": "9",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2008,
        9,
        1
      ]
    ]
  },
  "abstract": "<jats:p>Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC). The role of betapapillomaviruses in the development of cutaneous SCC is, however, still enigmatic. The ability to inhibit UVB-induced apoptosis, as demonstrated for HPV5 <jats:italic>in vitro</jats:italic>, may be important in this respect, as survival of DNA-damaged and mutated cells increases the risk of transformation. The aim of this study was to assess whether inhibition of UVB-induced apoptosis is a general property of betapapillomaviruses and to identify apoptotic factors that are potentially involved in this process. Primary human keratinocytes transduced with E6 and E7 of selected betapapillomaviruses (HPV5, HPV8, HPV15, HPV20, HPV24 and HPV38) were characterized and subjected to UVB irradiation. HPV8- and HPV20-expressing keratinocytes in particular showed fewer signs of apoptosis, as demonstrated by lower levels of active caspase 3, less enzymic caspase activity and less DNA fragmentation. The observed inhibition of UVB-induced apoptosis was mediated by E6 and coincided with reduced steady-state expression of the pro-apoptotic protein Bax. In conclusion, E6 of HPV8 and HPV20 reduces the apoptotic responses upon UVB irradiation when expressed in primary human keratinocytes. Infections with HPV8 and HPV20 may therefore augment the carcinogenic effect of UV radiation and potentially contribute to oncogenic transformation of the skin.</jats:p>",
  "DOI": "10.1099/vir.0.83317-0",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2008,
        8,
        27
      ]
    ],
    "date-time": "2008-08-27T15:45:58Z",
    "timestamp": 1219851958000
  },
  "page": "2303-2314",
  "source": "Crossref",
  "is-referenced-by-count": 54,
  "title": "Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes",
  "prefix": "10.1099",
  "volume": "89",
  "author": [
    {
      "given": "Linda",
      "family": "Struijk",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"
        }
      ]
    },
    {
      "given": "Els",
      "family": "van der Meijden",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"
        }
      ]
    },
    {
      "given": "Siamaque",
      "family": "Kazem",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"
        }
      ]
    },
    {
      "given": "Jan",
      "family": "ter Schegget",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"
        }
      ]
    },
    {
      "given": "Frank R.",
      "family": "de Gruijl",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands"
        }
      ]
    },
    {
      "given": "Renske D. M.",
      "family": "Steenbergen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands"
        }
      ]
    },
    {
      "given": "Mariet C. W.",
      "family": "Feltkamp",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"
        }
      ]
    }
  ],
  "member": "345",
  "reference": [
    {
      "key": "R1",
      "doi-asserted-by": "crossref",
      "first-page": "334",
      "DOI": "10.1038/sj.embor.7400615",
      "article-title": "Skin human papillomavirus type 38 alters p53 functions by accumulation of \u0394Np73",
      "volume": "7",
      "author": "Accardi",
      "year": "2006",
      "journal-title": "EMBO Rep"
    },
    {
      "key": "R2",
      "doi-asserted-by": "crossref",
      "first-page": "383",
      "DOI": "10.1006/viro.1999.9675",
      "article-title": "HPV16 E6 oncoprotein inhibits apoptosis induced during serum-calcium differentiation of foreskin human keratinocytes",
      "volume": "257",
      "author": "Alfandari",
      "year": "1999",
      "journal-title": "Virology"
    },
    {
      "key": "R3",
      "doi-asserted-by": "crossref",
      "first-page": "2639",
      "DOI": "10.1056/NEJMp048086",
      "article-title": "Milk of human kindness? \u2013 HAMLET, human papillomavirus, and warts",
      "volume": "350",
      "author": "Bouwes Bavinck",
      "year": "2004",
      "journal-title": "N Engl J Med"
    },
    {
      "key": "R4",
      "doi-asserted-by": "crossref",
      "first-page": "118",
      "DOI": "10.1002/(SICI)1097-0215(20000401)86:1<118::AID-IJC18>3.0.CO;2-2",
      "article-title": "Case\u2013control study in a subtropical Australian population to assess the relation between non-melanoma skin cancer and epidermodysplasia verruciformis human papillomavirus DNA in plucked eyebrow hairs",
      "volume": "86",
      "author": "Boxman",
      "year": "2000",
      "journal-title": "The Nambour Skin Cancer Prevention Study Group. Int J Cancer"
    },
    {
      "key": "R5",
      "doi-asserted-by": "crossref",
      "first-page": "1108",
      "DOI": "10.1046/j.1523-1747.2001.01499.x",
      "article-title": "Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses",
      "volume": "117",
      "author": "Boxman",
      "year": "2001",
      "journal-title": "J Invest Dermatol"
    },
    {
      "key": "R6",
      "doi-asserted-by": "crossref",
      "first-page": "821",
      "DOI": "10.1038/sj.onc.1203375",
      "article-title": "Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein",
      "volume": "19",
      "author": "Caldeira",
      "year": "2000",
      "journal-title": "Oncogene"
    },
    {
      "key": "R7",
      "doi-asserted-by": "crossref",
      "first-page": "2195",
      "DOI": "10.1128/JVI.77.3.2195-2206.2003",
      "article-title": "The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties",
      "volume": "77",
      "author": "Caldeira",
      "year": "2003",
      "journal-title": "J Virol"
    },
    {
      "key": "R8",
      "doi-asserted-by": "crossref",
      "first-page": "23",
      "DOI": "10.1111/j.0906-6705.2005.00384.x",
      "article-title": "Apoptosis induced by ultraviolet B in HPV-immortalized human keratinocytes requires caspase-9 and is death receptor independent",
      "volume": "15",
      "author": "Daher",
      "year": "2006",
      "journal-title": "Exp Dermatol"
    },
    {
      "key": "R9",
      "doi-asserted-by": "crossref",
      "first-page": "1792",
      "DOI": "10.1128/JCM.44.5.1792-1800.2006",
      "article-title": "Evaluation of a novel highly sensitive, broad-spectrum PCR-reverse hybridization assay for detection and identification of beta-papillomavirus DNA",
      "volume": "44",
      "author": "de Koning",
      "year": "2006",
      "journal-title": "J Clin Microbiol"
    },
    {
      "key": "R10",
      "doi-asserted-by": "crossref",
      "first-page": "1489",
      "DOI": "10.1099/vir.0.82732-0",
      "article-title": "Betapapillomaviruses frequently persist in the skin of healthy individuals",
      "volume": "88",
      "author": "de Koning",
      "year": "2007",
      "journal-title": "J Gen Virol"
    },
    {
      "key": "R11",
      "doi-asserted-by": "crossref",
      "first-page": "17",
      "DOI": "10.1016/j.virol.2004.03.033",
      "article-title": "Classification of papillomaviruses",
      "volume": "324",
      "author": "de Villiers",
      "year": "2004",
      "journal-title": "Virology"
    },
    {
      "key": "R12",
      "doi-asserted-by": "crossref",
      "first-page": "14899",
      "DOI": "10.1128/JVI.79.23.14899-14908.2005",
      "article-title": "Skin hyperproliferation and susceptibility to chemical carcinogenesis in transgenic mice expressing E6 and E7 of human papillomavirus type 38",
      "volume": "79",
      "author": "Dong",
      "year": "2005",
      "journal-title": "J Virol"
    },
    {
      "key": "R13",
      "first-page": "2695",
      "article-title": "Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer",
      "volume": "63",
      "author": "Feltkamp",
      "year": "2003",
      "journal-title": "Cancer Res"
    },
    {
      "key": "R14",
      "doi-asserted-by": "crossref",
      "first-page": "21730",
      "DOI": "10.1074/jbc.M200113200",
      "article-title": "The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis",
      "volume": "277",
      "author": "Filippova",
      "year": "2002",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "R15",
      "doi-asserted-by": "crossref",
      "first-page": "25729",
      "DOI": "10.1074/jbc.M401172200",
      "article-title": "The human papillomavirus 16 E6 protein binds to Fas-associated death domain and protects cells from Fas-triggered apoptosis",
      "volume": "279",
      "author": "Filippova",
      "year": "2004",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "R16",
      "doi-asserted-by": "crossref",
      "first-page": "2203",
      "DOI": "10.1038/sj.bjc.6601829",
      "article-title": "Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomavirus types 5 and 18",
      "volume": "90",
      "author": "Giampieri",
      "year": "2004",
      "journal-title": "Br J Cancer"
    },
    {
      "key": "R17",
      "doi-asserted-by": "crossref",
      "first-page": "2317",
      "DOI": "10.1002/ijc.22591",
      "article-title": "Selective induction of apoptosis by leptomycin B in keratinocytes expressing oncogenes",
      "volume": "120",
      "author": "Gray",
      "year": "2007",
      "journal-title": "Int J Cancer"
    },
    {
      "key": "R18",
      "doi-asserted-by": "crossref",
      "first-page": "101",
      "DOI": "10.1097/00001432-200204000-00002",
      "article-title": "Human papillomaviruses and non-melanoma skin cancer",
      "volume": "15",
      "author": "Harwood",
      "year": "2002",
      "journal-title": "Curr Opin Infect Dis"
    },
    {
      "key": "R19",
      "doi-asserted-by": "crossref",
      "first-page": "123",
      "DOI": "10.1046/j.1523-1747.1998.00240.x",
      "article-title": "Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers",
      "volume": "111",
      "author": "Harwood",
      "year": "1998",
      "journal-title": "J Invest Dermatol"
    },
    {
      "key": "R20",
      "doi-asserted-by": "crossref",
      "first-page": "289",
      "DOI": "10.1002/1096-9071(200007)61:3<289::AID-JMV2>3.0.CO;2-Z",
      "article-title": "Human papillomavirus infection and non-melanoma skin cancer in immunosuppressed and immunocompetent individuals",
      "volume": "61",
      "author": "Harwood",
      "year": "2000",
      "journal-title": "J Med Virol"
    },
    {
      "key": "R21",
      "doi-asserted-by": "crossref",
      "first-page": "4741",
      "DOI": "10.1093/emboj/cdf443",
      "article-title": "Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1",
      "volume": "21",
      "author": "Iftner",
      "year": "2002",
      "journal-title": "EMBO J"
    },
    {
      "key": "R22",
      "doi-asserted-by": "crossref",
      "first-page": "592",
      "DOI": "10.1038/sj.onc.1203339",
      "article-title": "E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage",
      "volume": "19",
      "author": "Jackson",
      "year": "2000",
      "journal-title": "Oncogene"
    },
    {
      "key": "R23",
      "doi-asserted-by": "crossref",
      "first-page": "3065",
      "DOI": "10.1101/gad.182100",
      "article-title": "Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins",
      "volume": "14",
      "author": "Jackson",
      "year": "2000",
      "journal-title": "Genes Dev"
    },
    {
      "key": "R24",
      "doi-asserted-by": "crossref",
      "first-page": "389",
      "DOI": "10.1093/jnci/djj092",
      "article-title": "Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin",
      "volume": "98",
      "author": "Karagas",
      "year": "2006",
      "journal-title": "J Natl Cancer Inst"
    },
    {
      "key": "R25",
      "doi-asserted-by": "crossref",
      "first-page": "549",
      "DOI": "10.1007/s10495-006-0004-1",
      "article-title": "Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria",
      "volume": "12",
      "author": "Leverrier",
      "year": "2007",
      "journal-title": "Apoptosis"
    },
    {
      "key": "R26",
      "doi-asserted-by": "crossref",
      "first-page": "611",
      "DOI": "10.1099/vir.0.80453-0",
      "article-title": "Downregulation of Bax mRNA expression and protein stability by the E6 protein of human papillomavirus 16",
      "volume": "86",
      "author": "Magal",
      "year": "2005",
      "journal-title": "J Gen Virol"
    },
    {
      "key": "R27",
      "first-page": "323",
      "article-title": "Cellular transformation by papillomavirus oncoproteins",
      "volume": "1155",
      "author": "Mansur",
      "year": "1993",
      "journal-title": "Biochim Biophys Acta"
    },
    {
      "key": "R28",
      "doi-asserted-by": "crossref",
      "first-page": "890",
      "DOI": "10.1001/archderm.139.7.890",
      "article-title": "Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals",
      "volume": "139",
      "author": "Masini",
      "year": "2003",
      "journal-title": "Arch Dermatol"
    },
    {
      "key": "R29",
      "doi-asserted-by": "crossref",
      "first-page": "11153",
      "DOI": "10.1128/JVI.00954-06",
      "article-title": "E6/E7 expression of human papillomavirus type 20 (HPV-20) and HPV-27 influences proliferation and differentiation of the skin in UV-irradiated SKH-hr1 transgenic mice",
      "volume": "80",
      "author": "Michel",
      "year": "2006",
      "journal-title": "J Virol"
    },
    {
      "key": "R30",
      "doi-asserted-by": "crossref",
      "first-page": "401",
      "DOI": "10.1111/j.0906-6705.2005.00296.x",
      "article-title": "E6* oncoprotein expression of human papillomavirus type-16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defence",
      "volume": "14",
      "author": "Mouret",
      "year": "2005",
      "journal-title": "Exp Dermatol"
    },
    {
      "key": "R31",
      "doi-asserted-by": "crossref",
      "first-page": "1340",
      "DOI": "10.1111/j.1349-7006.1991.tb01802.x",
      "article-title": "Tumorigenic transformation of primary rat embryonal fibroblasts by human papillomavirus type 8 E7 gene in collaboration with the activated H-ras gene",
      "volume": "82",
      "author": "Nishikawa",
      "year": "1991",
      "journal-title": "Jpn J Cancer Res"
    },
    {
      "key": "R32",
      "doi-asserted-by": "crossref",
      "first-page": "425",
      "DOI": "10.1373/49.3.425",
      "article-title": "PCR-based calibration curves for studies of quantitative gene expression in human monocytes: development and evaluation",
      "volume": "49",
      "author": "Ovstebo",
      "year": "2003",
      "journal-title": "Clin Chem"
    },
    {
      "key": "R33",
      "doi-asserted-by": "crossref",
      "first-page": "273",
      "DOI": "10.1007/s00403-003-0435-2",
      "article-title": "High prevalence of epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population",
      "volume": "295",
      "author": "Pfister",
      "year": "2003",
      "journal-title": "Arch Dermatol Res"
    },
    {
      "key": "R34",
      "doi-asserted-by": "crossref",
      "first-page": "1394",
      "DOI": "10.1158/0008-5472.CAN-04-3263",
      "article-title": "Development of skin tumors in mice transgenic for early genes of human papillomavirus type 8",
      "volume": "65",
      "author": "Schaper",
      "year": "2005",
      "journal-title": "Cancer Res"
    },
    {
      "key": "R35",
      "doi-asserted-by": "crossref",
      "first-page": "7051",
      "DOI": "10.1128/JVI.68.11.7051-7059.1994",
      "article-title": "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",
      "volume": "68",
      "author": "Schmitt",
      "year": "1994",
      "journal-title": "J Virol"
    },
    {
      "key": "R36",
      "doi-asserted-by": "crossref",
      "first-page": "24709",
      "DOI": "10.1074/jbc.M200281200",
      "article-title": "HPV-16 E6/7 immortalization sensitizes human keratinocytes to ultraviolet B by altering the pathway from caspase-8 to caspase-9-dependent apoptosis",
      "volume": "277",
      "author": "Simbulan-Rosenthal",
      "year": "2002",
      "journal-title": "J Biol Chem"
    },
    {
      "issue": "Suppl. 1",
      "key": "R37",
      "doi-asserted-by": "crossref",
      "first-page": "S25",
      "DOI": "10.1016/j.jcv.2004.11.019",
      "article-title": "HPV-mediated transformation of the anogenital tract",
      "volume": "32",
      "author": "Steenbergen",
      "year": "2005",
      "journal-title": "J Clin Virol"
    },
    {
      "key": "R38",
      "doi-asserted-by": "crossref",
      "first-page": "1531",
      "DOI": "10.1046/j.1523-1747.2003.12632.x",
      "article-title": "Presence of human papillomavirus DNA in plucked eyebrow hairs is associated with a history of cutaneous squamous cell carcinoma",
      "volume": "121",
      "author": "Struijk",
      "year": "2003",
      "journal-title": "J Invest Dermatol"
    },
    {
      "key": "R39",
      "doi-asserted-by": "crossref",
      "first-page": "2943",
      "DOI": "10.1038/sj.onc.1202223",
      "article-title": "Inhibition of Bak-induced apoptosis by HPV-18 E6",
      "volume": "17",
      "author": "Thomas",
      "year": "1998",
      "journal-title": "Oncogene"
    },
    {
      "key": "R40",
      "doi-asserted-by": "crossref",
      "first-page": "1513",
      "DOI": "10.1099/0022-1317-80-6-1513",
      "article-title": "Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types",
      "volume": "80",
      "author": "Thomas",
      "year": "1999",
      "journal-title": "J Gen Virol"
    },
    {
      "key": "R41",
      "doi-asserted-by": "crossref",
      "first-page": "4009",
      "DOI": "10.1038/sj.onc.1209429",
      "article-title": "Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein",
      "volume": "25",
      "author": "Vogt",
      "year": "2006",
      "journal-title": "Oncogene"
    },
    {
      "key": "R42",
      "first-page": "2433",
      "article-title": "Biological and biochemical activity of E7 genes of the cutaneous human papillomavirus type 5 and 8",
      "volume": "8",
      "author": "Yamashita",
      "year": "1993",
      "journal-title": "Oncogene"
    },
    {
      "key": "R43",
      "doi-asserted-by": "crossref",
      "first-page": "342",
      "DOI": "10.1038/nrc798",
      "article-title": "Papillomaviruses and cancer: from basic studies to clinical application",
      "volume": "2",
      "author": "zur Hausen",
      "year": "2002",
      "journal-title": "Nat Rev Cancer"
    }
  ],
  "container-title": "Journal of General Virology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.83317-0?crawler=true",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2020,
        11,
        4
      ]
    ],
    "date-time": "2020-11-04T12:42:19Z",
    "timestamp": 1604493739000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.83317-0"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2008,
        9,
        1
      ]
    ]
  },
  "references-count": 43,
  "journal-issue": {
    "issue": "9",
    "published-print": {
      "date-parts": [
        [
          2008,
          9,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1099/vir.0.83317-0",
  "relation": {},
  "ISSN": [
    "0022-1317",
    "1465-2099"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2008,
        9,
        1
      ]
    ]
  }
}