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Cell Jul 2021We study a patient with the human papilloma virus (HPV)-2-driven "tree-man" phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an...
We study a patient with the human papilloma virus (HPV)-2-driven "tree-man" phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an HPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes in the epidermis basal layer. The patients are unexpectedly homozygous for a private CD28 variant. They have no detectable CD28 on their T cells, with the exception of a small contingent of revertant memory CD4 T cells. T cell development is barely affected, and T cells respond to CD3 and CD2, but not CD28, costimulation. Although the patients do not display HPV-2- and HPV-4-reactive CD4 T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cell CD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses are largely redundant for protective immunity.
Topics: Adult; Amino Acid Sequence; Animals; Base Sequence; CD28 Antigens; CD4-Positive T-Lymphocytes; Child; Endopeptidases; Female; Genes, Recessive; HEK293 Cells; Homozygote; Humans; Immunity, Humoral; Immunologic Memory; Inheritance Patterns; Jurkat Cells; Keratinocytes; Male; Mice, Inbred C57BL; Oncogenes; Papilloma; Papillomaviridae; Pedigree; Protein Sorting Signals; RNA, Messenger; Skin; T-Lymphocytes; Mice
PubMed: 34214472
DOI: 10.1016/j.cell.2021.06.004 -
Veterinary Microbiology Feb 2024The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal... (Review)
Review
The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal health. Although more than 250 species have been described in humans, the total number of papillomaviruses (PVs) discovered in animals does not reach up to this number. In animals, PV infections are mostly asymptomatic or can cause variable clinical conditions ranging from self-limiting papillomas and other cutaneous and mucosal benign lesions to cancer. Most of animal PV types have been discovered in cattle, dogs, horses, and cats with other farm host species remaining overlooked. In particular, the number of PV types so far identified in sheep is limited. This paper comprehensively reviews ovine PVs features, including viral taxonomy and evolution; genome organization; viral tropism and pathogenesis; macroscopical features and histopathological patterns, as well as available diagnostics tools. Data are critically presented and discussed in terms of impact on veterinary and public health. The development of future dedicated research is also discussed.
Topics: Animals; Deltapapillomavirus; Papilloma; Papillomaviridae; Papillomavirus Infections; Sheep; Sheep Diseases; Virulence
PubMed: 38160507
DOI: 10.1016/j.vetmic.2023.109955 -
Indian Journal of Dental Research :... 2010Cowden syndrome or multiple hamartoma syndrome is an autosomal dominant condition with variable expressions that result mainly from mutation in the PTEN gene on arm 10q....
Cowden syndrome or multiple hamartoma syndrome is an autosomal dominant condition with variable expressions that result mainly from mutation in the PTEN gene on arm 10q. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal tract, bones, CNS, eyes, and genitourinary tract. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here we present a case of Cowden syndrome in a 14-year-old female patient with the chief complaint of multiple oral papillomatous lesions.
Topics: Adolescent; Female; Gingival Neoplasms; Hamartoma Syndrome, Multiple; Humans; Mouth Mucosa; Mouth Neoplasms; Papilloma; Tongue Neoplasms
PubMed: 20930359
DOI: 10.4103/0970-9290.70803 -
Cell Death and Differentiation Apr 2023Non-melanoma skin cancer (NMSC) has risen dramatically as a result of chronic exposure to sunlight ultraviolet (UV) radiation, climatic changes and clinical conditions...
Non-melanoma skin cancer (NMSC) has risen dramatically as a result of chronic exposure to sunlight ultraviolet (UV) radiation, climatic changes and clinical conditions associated with immunosuppression. In spite of considerable progress, our understanding of the mechanisms that control NMSC development and their associated molecular and immunological landscapes is still limited. Here we demonstrated a critical role for galectin-7 (Gal-7), a β-galactoside-binding protein preferentially expressed in skin tissue, during NMSC development. Transgenic mice (Tg46) overexpressing Gal-7 in keratinocytes showed higher number of papillomas compared to WT mice or mice lacking Gal-7 (Lgals7) when subjected to a skin carcinogenesis protocol, in which tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were sequentially administered. RNAseq analysis of Tg46 tumor lesions revealed a unique profile compatible with cells of the myelomonocytic lineage infiltrating these tumors, an effect that was substantiated by a higher number of CD11bGr1 cells in tumor-draining lymph nodes. Heightened c-Met activation and Cxcl-1 expression in Tg46 lesions suggested a contribution of this pathway to the recruitment of these cells. Remarkably, Gal-7 bound to the surface of CD11bLy6CLy6G monocytic myeloid cells and enhanced their immunosuppressive activity, as evidenced by increased IL-10 and TGF-β secretion, and higher T-cell inhibitory activity. In vivo, carcinogen-treated Lgals7 animals adoptively transferred with Gal-7-conditioned monocytic myeloid cells developed higher number of papillomas, whereas depletion of these cells in Tg46-treated mice led to reduction in the number of tumors. Finally, human NMSC biopsies showed increased LGALS7 mRNA and Gal-7 protein expression and displayed transcriptional profiles associated with myeloid programs, accompanied by elevated CXCL1 expression and c-Met activation. Thus, Gal-7 emerges as a critical mediator of skin carcinogenesis and a potential therapeutic target in human NMSC.
Topics: Mice; Animals; Humans; Carcinogens; Skin Neoplasms; Papilloma; Carcinogenesis; Mice, Transgenic; Galectins; Skin; Immunity, Innate
PubMed: 36693903
DOI: 10.1038/s41418-022-01108-7 -
Deutsches Arzteblatt International Aug 2022
Topics: Humans; Papilloma; Skin
PubMed: 36384928
DOI: 10.3238/arztebl.m2022.0088 -
Biomedicine & Pharmacotherapy =... Oct 2023Sirtuin 6 (SIRT6) has a critical role in cutaneous Squamous Cell Carcinoma (cSCC): SIRT6 silencing in skin SCC cells has pro-differentiating effects and SIRT6 deletion...
Sirtuin 6 (SIRT6) has a critical role in cutaneous Squamous Cell Carcinoma (cSCC): SIRT6 silencing in skin SCC cells has pro-differentiating effects and SIRT6 deletion abrogated DMBA-TPA-induced skin tumorigenesis in mice. On the other hand, SIRT6 acts as tumor suppressor in SCC by enhancing glycolysis in tumor propagating cells. Herein, pharmacological modulation of SIRT6 deacetylase activity was investigated in cSCC, with S6 (inhibitor) or MDL-800 (activator). In cSCC cells, S6 recreated the pro-differentiating effects of SIRT6 silencing, as the levels of Keratin 1, Keratin 10 and Loricrin were upregulated compared to controls. Next, the effects of SIRT6 pharmacological modulation were evaluated in a DMBA-TPA-induced skin cancer mouse model. Mice treated with the inhibitor S6 in a preventive approach, i.e. at the beginning of the promotion stage, presented reduced number and size of papillomas, compared to the controls. The epidermal hyperproliferation marker Keratin 6 and the cSCC marker Keratin 8 were less abundant when SIRT6 was inhibited. In S6-treated lesions, the Epithelial-Mesenchymal Transition (EMT) markers Zeb1 and Vimentin were less expressed compared to untreated lesions. In a therapeutic approach, i.e. treatment starting after papilloma appearance, the S6 group presented reduced papillomas (number and size), whereas MDL-800-treated mice displayed an opposite trend. In S6-treated lesions, Keratin 6 and Keratin 8 were less expressed, EMT was less advanced, with a higher E-cadherin/Vimentin ratio, indicating a delayed carcinogenesis when SIRT6 was inhibited. Our results confirm that SIRT6 plays a role in skin carcinogenesis and suggest SIRT6 pharmacological inhibition as a promising strategy in cSCC.
Topics: Animals; Mice; Skin Neoplasms; Carcinoma, Squamous Cell; Keratin-8; Vimentin; Keratin-6; Papilloma; Carcinogenesis; Sirtuins
PubMed: 37611438
DOI: 10.1016/j.biopha.2023.115326 -
Viruses Feb 2020Papillomavirus (PV) mainly infects the squamous epithelium and may potentially lead to benign or even malignant cutaneous lesions. However, the malignant transforming...
Papillomavirus (PV) mainly infects the squamous epithelium and may potentially lead to benign or even malignant cutaneous lesions. However, the malignant transforming ability has been identified in several types of PVs. In humans, papillomavirus (HPV) type 16 and 18 are the most prevalent causative agents of cervical cancer. Therefore, vaccines are being developed to protect against these types. For dogs, there have been limited investigations into the association of different canine papillomavirus (CPV) genotypes with malignant lesions. Understanding the high-risk CPV genotype(s) responsible for these malignant lesions would contribute to the development of interventions for preventing CPV-induced carcinomas. In the present study, a retrospective cohort of 102 pathologically confirmed papillomas and 212 squamous cell carcinomas (SCCs) were included. The viral genome and antigens in the formalin-fixed paraffin-embedded (FFPE) tissues were detected using PCR targeting pan PV E1 and COPV L1 genes and by immunohistochemistry staining (IHC), respectively. PVs were successfully detected from 11 FFPE cutaneous tissues and four oral tissues using pan PV E1- and COPV L1-based PCR, respectively. After sequencing, CPV 1, CPV 2, and CPV 6 were detected in the benign lesions using PCR and were confirmed through IHC. While CPV 9 and CPV 15 were first detected in the SCCs of dogs, CPV 16 was most often detected in SCC specimens. The association and confirmative demonstration of viral genes and intralesional antigens of CPV 9, CPV 15, and CPV 16 in SCCs highlight the potential risk of these genotypes of CPVs in malignant transformation.
Topics: Animals; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA, Viral; Dog Diseases; Dogs; Immunohistochemistry; Papillomaviridae; Papillomavirus Infections; Paraffin Embedding; Retrospective Studies; Skin; Skin Neoplasms
PubMed: 32028559
DOI: 10.3390/v12020170 -
Molecular and Cellular Biology Aug 2018Using Sos1 knockout (Sos1-KO), Sos2-KO, and Sos1/2 double-knockout (Sos1/2-DKO) mice, we assessed the functional role of Sos1 and Sos2 in skin homeostasis under...
Using Sos1 knockout (Sos1-KO), Sos2-KO, and Sos1/2 double-knockout (Sos1/2-DKO) mice, we assessed the functional role of Sos1 and Sos2 in skin homeostasis under physiological and/or pathological conditions. Sos1 depletion resulted in significant alterations of skin homeostasis, including reduced keratinocyte proliferation, altered hair follicle and blood vessel integrity in dermis, and reduced adipose tissue in hypodermis. These defects worsened significantly when both Sos1 and Sos2 were absent. Simultaneous Sos1/2 disruption led to severe impairment of the ability to repair skin wounds, as well as to almost complete ablation of the neutrophil-mediated inflammatory response in the injury site. Furthermore, Sos1 disruption delayed the onset of tumor initiation, decreased tumor growth, and prevented malignant progression of papillomas in a DMBA (7,12-dimethylbenz[α]anthracene)/TPA (12--tetradecanoylphorbol-13-acetate)-induced skin carcinogenesis model. Finally, Sos1 depletion in preexisting chemically induced papillomas resulted also in decreased tumor growth, probably linked to significantly reduced underlying keratinocyte proliferation. Our data unveil novel, distinctive mechanistic roles of Sos 1 and Sos2 in physiological control of skin homeostasis and wound repair, as well as in pathological development of chemically induced skin tumors. These observations underscore the essential role of Sos proteins in cellular proliferation and migration and support the consideration of these RasGEFs as potential biomarkers/therapy targets in Ras-driven epidermal tumors.
Topics: Animals; Carcinogenesis; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Homeostasis; Mice; Mice, Knockout; Neovascularization, Physiologic; Papilloma; SOS1 Protein; Skin; Skin Neoplasms; Son of Sevenless Proteins; Wound Healing
PubMed: 29844066
DOI: 10.1128/MCB.00049-18 -
Indian Journal of Dermatology,... 2010Vulvar vestibular papillomatosis is considered an anatomical variant of the vulva. Recognition of this condition enables one to distinguish it from warts and therefore...
Vulvar vestibular papillomatosis is considered an anatomical variant of the vulva. Recognition of this condition enables one to distinguish it from warts and therefore avoid unnecessary therapy. A 29-year-old lady presented to this clinic with a history of 'small growths' in her vulva since two years. Examination identified skin colored translucent papules; some of them appeared digitate and were seen on the vestibule and inner aspect of both labia minora. They were soft to feel and non-tender. Few lesions looked like elongated pearly penile papules. A provisional diagnosis of vestibular papillomatosis was made and a biopsy was done. It showed finger-like protrusions of loosely arranged subdermal tissue with blood vessels and which were covered by normal mucosal epithelium. No koilocytes were seen and the diagnosis of vestibular papillomatosis was confirmed. We believe that this is the first case report of vulvar vestibular papillomatosis in Indian dermatologic literature.
Topics: Adult; Female; Humans; Papilloma; Vulvar Neoplasms
PubMed: 20445299
DOI: 10.4103/0378-6323.62971 -
The Journal of Veterinary Medical... Nov 2021Skin lesions possibly caused by Papillomavirus infections in two four-toed hedgehogs are described. In case 1, there was a papillary mass on the right hind limb....
Skin lesions possibly caused by Papillomavirus infections in two four-toed hedgehogs are described. In case 1, there was a papillary mass on the right hind limb. Histologically, the mass was consistent with a viral papilloma. In the other case, multifocal papillary masses with erosions and ulcers were found throughout the body, mainly on the extremities. Histology showed continuative lesions composed of acanthosis, Bowenoid in situ carcinoma, and squamous cell carcinoma, with abrupt transitions between the lesions. In both cases, keratinocytes in the granular layer infrequently had features of koilocytes and intranuclear inclusion bodies, and immunohistochemical staining was positive for anti-human papillomavirus antibody. To the best of the authors' knowledge, this is the first pathological documentation of possibly papillomavirus-associated skin lesions in four-toed hedgehogs.
Topics: Animals; Carcinoma, Squamous Cell; Hedgehogs; Papilloma
PubMed: 34544958
DOI: 10.1292/jvms.21-0302