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  • 1
    Keywords: CANCER ; CELLS ; BLOOD ; CELL ; Germany ; human ; IN-VIVO ; MODEL ; VIVO ; SYSTEM ; incidence ; RISK ; HYBRIDIZATION ; TUMORS ; DNA ; INFECTION ; IMPACT ; CARCINOGENESIS ; RAT ; animals ; tumour ; SKIN ; papillomavirus ; TARGET ; TRANSGENIC MICE ; IN-SITU ; skin cancer ; LINE ; E6 ; BENIGN ; STEM-CELLS ; TARGET-CELLS ; INVOLVEMENT ; SQUAMOUS-CELL CARCINOMAS ; TARGETS ; INFECTIONS ; SKIN-CANCER ; FOLLICLE ; in situ hybridization ; HUMAN CANCER ; HAIR FOLLICLE ; RECIPIENTS ; LIFE-CYCLE ; development ; chemical carcinogenesis ; PERSISTENCE ; HUMAN CANCERS ; CANCERS ; in vivo ; PREDICTOR ; animal ; microbiology ; viral ; virology ; Mothers ; biotechnology ; GENOMES
    Abstract: The high incidence of multiple wart formation and skin cancer in organ-transplant recipients, as well as the question of an involvement of papillomaviruses in a variety of human cancers, require a model system for papillomavirus infections in immunocompetent animals. Such an in vivo model is represented by the multimammate rat Mastomys coucha, which is infected with Mastomys natalensis papillomavirus (MnPV). MnPV primarily induces benign skin tumours, such as papillomas and keratoacanthomas. Here, the incidence of MnPV infections in different skin areas and various organs is described. In situ hybridization showed that hair follicle cells were positive for viral DNA and that the amount of MnPV in normal skin may be considered a predictor for the development of skin tumours. MnPV infection is not restricted to the skin, but can also be detected in inner organs. As the blood and the lymphatic system were temporarily also found to be virus-positive, a haematogenic propagation of MnPV can be assumed. However, MnPV is apparently not transmitted through the germ line, as fetuses and newborns lack viral DNA, despite infection of their mothers. In conclusion, M. coucha is not only useful to study papillomavirus-induced skin carcinogenesis, but may also serve as a model to identify additional, still unknown target cells of papillomavirus infections and the potential pathological impact
    Type of Publication: Journal article published
    PubMed ID: 17872518
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  • 2
    Keywords: CELLS ; CELL ; COMBINATION ; Germany ; GENE ; GENES ; GENOME ; PROTEINS ; COMPLEX ; COMPLEXES ; SKIN ; papillomavirus ; ACID ; EVOLUTION ; L1 ; PHYLOGENETIC ANALYSIS ; AMINO-ACID ; hair ; LONG ; adaptation ; GENOMES ; SEQUENCE DATA ; EEPV
    Abstract: Knowledge about biological diversity is the prerequisite to reliably reconstruct the evolution of pathogens such as papillomaviruses (PV). However, complete genomes of non-human PV have only been cloned and sequenced from 8 out of 18 orders within the Placentalia, although the host-specific variety of PV is considered much larger. We isolated and sequenced the complete genome of the first insectivoran PV type from hair follicle cells of the European hedgehog (Erinaceus europaeus), designated EHPV. We conducted phylogenetic analyses (maximum-likelihood criterion and Bayesian inference) with the genomic information of a systematically representative set of 67 PV types including EHPV As inferred from amino acid sequence data of the separate genes E1, E2 and L1 as well as of the gene combination E6-E7-E1-E2-L1, EHPV clustered within the beta-gamma-pi-zeta-PV supertaxon and constituted the closest relative of genus Betapapillomavirus infecting primates. Beside the typical organization of the PV genome, EHPV exhibited a 1172 lop, non-coding region between the E2 and the L2 open reading frames. This trait has been previously described for the only distantly related Lambdapapillomavirus, but a common evolutionary origin of both non-coding regions is unlikely. Our results underscore the modular organization of the PV genome and the complex natural history of PV
    Type of Publication: Journal article published
    PubMed ID: 19218207
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  • 3
    Keywords: SPECTRA ; CANCER ; Germany ; human ; SUPPORT ; COHORT ; GENOME ; PATIENT ; DNA ; INFECTION ; SKIN ; PCR ; HPV ; BETA ; PREVALENCE ; immunosuppression ; SKIN-CANCER ; papillomaviruses ; GAMMA ; RECIPIENTS ; VIRAL LOAD ; allergy ; cutaneous HPV ; HUMAN PAPILLOMAVIRUSES ; HPV types ; 33 ; ALLERGIES ; organ transplant recipients ; RANGE ; cutaneous warts
    Abstract: BACKGROUND: A broad spectrum of human papillomaviruses (HPV) has been detected in warts from immunocompetent patients and a much more diverse range from immunosuppressed organ transplant recipients (OTR). OBJECTIVES: To determine the HPV types in warts from OTR, we assessed present infections of mucosal (alpha-PV), wart-associated (alpha-, micro- and nu-PV) and cutaneous HPV types (beta-/gamma-PV) in immunocompetent patients and OTR. Patients/methods Forty-one warts from 29 immunocompetent patients (non-OTR) and 53 warts from 33 OTR were analysed for DNA of human alpha-, beta-, gamma-, micro- and nu-PV. For frequent types viral load was determined by quantitative real-time PCR. RESULTS: Compared with non-OTR prevalence of cutaneous HPV (79% vs. 49%, P 〈 0.01) and the number of multiple infections (62% vs. 17%, P 〈 0.0001) were significantly increased. The mean viral load of the wart-associated HPV was more than 10(5)-fold higher compared with human beta-PV in both cohorts. CONCLUSIONS: The high load of wart-associated HPV suggests an active role of these viruses rather than cutaneous types in warts independent of immunosuppression; however, the substantial fraction of warts with low HPV genome copies remains to be explained.
    Type of Publication: Journal article published
    PubMed ID: 19519829
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  • 4
    Keywords: ACID, AMINO-ACID, animals, CANCER, CELL, CELLS, cluster analysis, DNA,Viral/chemistry/genetics, Evol
    Abstract: A series of papillomavirus (PV) types have been isolated from different rodent species, and most of them belong to the genus Pipapillomavirus. We isolated and sequenced the complete genome of a novel PV type (designated RnPV) from the oral cavity of the Norway rat (Rattus norvegicus), as well as an L1 gene fragment from hair-follicle cells of the European beaver (Castor fiber). As inferred from amino acid sequence data, RnPV clustered within the beta+gamma+pi+Xi-PV supertaxon as a member of the genus Pipapillomavirus. The closest relatives of RnPV were McPV-2 and MmPV, and time estimates indicated that the genus Pipapillomavirus originated in the late Cenozoic era. The close relationship of RnPV to other murid PV types supports the hypothesis of co-divergence between members of the genus Pipapillomavirus and their hosts. However, the derived Neogene origin of the genus Pipapillomavirus is much younger than has been considered for the Rodentia as the primary hosts, indicating that alternative interpretations of the phylogenetic trees should be conceived.
    Type of Publication: Journal article published
    PubMed ID: 19605590
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  • 5
    Keywords: CANCER ; tumor ; carcinoma ; CELL ; Germany ; POPULATION ; RISK ; TUMORS ; MARKER ; LIVER-TRANSPLANTATION ; RISK-FACTORS ; CARCINOGENESIS ; SKIN ; ASSOCIATION ; IDENTIFICATION ; LESIONS ; NUMBER ; AGE ; risk factors ; skin cancer ; MELANOMA ; RISK FACTOR ; human papillomavirus ; SURVEILLANCE ; HPV ; ONCOGENE ; CARCINOMAS ; IMMUNITY ; skin tumors ; MANAGEMENT ; HPV INFECTION ; papillomaviruses ; RECIPIENTS ; TRANSPLANT RECIPIENTS ; development ; ACTINIC KERATOSES ; NONMELANOMA SKIN-CANCER ; HEPATITIS-C ; SQUAMOUS-CELL ; KERATOSES ; cutaneous warts ; IMMUNE ; CELL CARCINOMAS ; IMMUNOSUPPRESSED PATIENTS ; FLUORINATED PYRIMIDINES ; Organ transplant ; RENAL-ALLOGRAFT RECIPIENTS ; Verrucae vulgaris ; VIRAL WARTS
    Abstract: Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially indentifing patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charit, University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed
    Type of Publication: Journal article published
    PubMed ID: 20165825
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  • 6
    Keywords: CANCER ; CELLS ; AGENTS ; CELL ; Germany ; CLASSIFICATION ; HYBRIDIZATION ; INFECTION ; mechanisms ; SKIN ; papillomavirus ; IN-SITU ; AMPLIFICATION ; skin cancer ; HPV ; E6 ; ONCOPROTEIN ; PREVALENCE ; papillomaviruses ; RECIPIENTS ; TRANSPLANT RECIPIENTS ; SCIENCE ; development ; Phylogeny ; SKIN-LESIONS ; human papillomavirus (HPV) ; cutaneous warts ; COMMON WARTS ; Cutaneous ; IMMUNOSUPPRESSED PATIENTS ; Organ transplant recipients (OTR)
    Abstract: Warts from immunosuppressed organ transplant recipients (OTR) persist over years and may progress into non-melanoma skin cancer. Human papillomaviruses (HPV) are considered the causal agents for the development of such warts. We isolated the novel type HPV-117 from a persisting wart by rolling circle amplification. One hundred eighteen warts from immunocompetent patients (IC) and 49 warts from OTR were analyzed by HPV-117 E6 type-specific PCR. As inferred from a phylogenetic analysis, the new type HPV-117 belonged to alpha-PV species 2, including the most similar types HPV-10 and HPV-94. The general prevalence of HPV-117 in warts was 2% in IC (2/118), and 12% in OTR (6/49). The high viral load in dysplastic cells of a Verruca vulgaris was shown by in situ hybridization. Our results suggest an active role of the novel type in the development of cutaneous warts of OTR. (C) 2009 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 20096912
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  • 7
  • 8
    Keywords: CANCER ; GROWTH ; Germany ; MODEL ; SYSTEM ; DIFFERENTIATION ; TIME ; CARCINOGENESIS ; animals ; tumour ; SKIN ; papillomavirus ; treatment ; virus ; LESIONS ; RATES ; skin cancer ; BENIGN ; immune response ; IMMUNE-RESPONSE ; SKIN-CANCER ; GROWTH ARREST ; ARREST ; REGRESSION ; allergy ; methods ; ANIMAL-MODEL ; uptake ; animal ; keratoacanthoma ; animal model ; epithelial skin cancer ; BASAL-CELL CARCINOMA ; animal models ; CREAM ; imiquimod ; Mastomys coucha ; NATALENSIS PAPILLOMAVIRUS ; TOPICAL 5-PERCENT IMIQUIMOD
    Abstract: Background Immune response modifiers including imiquimod can be topically applied for the treatment of both genital warts and benign and malignant skin tumours (e.g. actinic keratosis). In an initial pilot study, we examined the response of spontaneously papillomavirus caused skin lesions (e.g. papillomas, keratoacanthomas) vs. chemically induced skin tumours of Mastomys coucha to imiquimod. Methods Fourteen spontaneously and 16 chemically [initiation with 7,12-dimethylbenzanthracene (DMBA) followed by repeated 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications] induced skin tumours were treated two to three times per week with 5% imiquimod or placebo. Results Notably, significant higher regression or growth arrest rates of imiquimod treated animals were observed in chemically vs. spontaneously induced skin tumours [9/14 (64%) vs. 2/11 (18%), P 〈 0.05]. Regression or growth arrest of both skin tumours from placebo treated animals were similar (1/2 vs. 1/3). Tumour growth of nonresponders was lowest in imiquimod treated animals compared to the placebo or untreated group. Conclusions Imiquimod was able to reduce skin tumour growth particularly in chemically induced lesions of Mastomys coucha. The different clearance rates are most likely due to lower differentiation status of the DMBA/TPA-induced tumours, allowing a better uptake of imiquimod than spontaneously induced papillomas or keratoacanthomas, known to be highly keratinized
    Type of Publication: Journal article published
    PubMed ID: 18067625
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  • 9
    Keywords: evaluation ; Germany ; SUPPORT ; CLONING ; DISTINCT ; GENE ; GENES ; radiation ; COMPLEX ; INFECTION ; MECHANISM ; animals ; BASE ; mechanisms ; papillomavirus ; SEQUENCE ; SEQUENCES ; TYPE-1 ; ACID ; virus ; genetics ; EVOLUTION ; BETA ; NETHERLANDS ; FRAGMENTS ; RENAL-TRANSPLANT RECIPIENTS ; heredity ; SKIN-CANCER ; molecular ; zoonosis ; LEVEL ; analysis ; methods ; EPITHELIUM ; FRAGMENT ; animal ; INFERENCE ; host ; adaptive radiation ; interspecies transmission ; BIRDS ; NUCLEOTIDE ; Co-evolution ; pathogene
    Abstract: The diversity of papillomaviruses (PVes) infecting stratified squamous epithelia of warm-blooded animals, such as birds and mammals, is only fragmentarily documented. The PV types are sequenced from 9 of 18 placental taxa at the order level to date. Current phylogenetic analyses of PV sequences frequently do not consider evolutionary polarity and statistical evaluation of internal nodes, that are required for robust evolutionary conclusions. In this study, we isolated and characterized three putatively novel animal PV types from hair follicles comprising the first known insectivoran PV and two cervid PVes. With the help of the primer pair FAP59/FAP64, we amplified L1 gene fragments consisting of approximately 470 base pairs. Phylogenetic analyses were performed with a representative set of 73 PV sequences that included the three novel PVes using Maximum Likelihood, Bayesian inference, Maximum Parsimony, and distance-based methods on amino acid alignments. The three novel PVes appear to be components of the beta+gamma+pi+xi-PV supertaxon, within which the insectivoran PV has an isolated phylogenetic position. The two cervid PVes constitute a distinct group that is only distantly related to the core cervid PVes of the delta-PVes. The molecular data supports a complex evolutionary scenario for PVes which is driven by multiple mechanisms comprising host-linked evolution, adaptive radiation establishing different ecological niches, and multiple infections across species borders
    Type of Publication: Journal article published
    PubMed ID: 18210195
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  • 10
    Keywords: CANCER ; RISK ; DNA ; ASSOCIATION ; case-control study ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; ACTINIC KERATOSES ; E6 PROTEINS ; NONMELANOMA SKIN-CANCER ; IMMUNOCOMPETENT INDIVIDUALS ; HUMAN-PAPILLOMAVIRUS TYPES ; cutaneous squamous cell carcinoma ; BETA-HUMAN PAPILLOMAVIRUSES ; Betapapillomavirus ; NATIONWIDE COHORT ; organ transplant recipient
    Abstract: We examined the association between betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (〉 94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0; 5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in
    Type of Publication: Journal article published
    PubMed ID: 21718442
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