title: Immune status, strain background, and anatomic site of inoculation affect mouse papillomavirus (MmuPV1) induction of exophytic papillomas or endophytic trichoblastomas.
abstract: Papillomaviruses (PVs) induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), was horizontally transmitted within an inbred colony of NMRI-Foxn1(nu)/Foxn1nu (nude; T cell deficient) mice of an unknown period of time. A ground-up, filtered papilloma inoculum was not capable of infecting C57BL/6J wild-type mice; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1(nu) and B6.Cg-Foxn1(nu), but not NU/J-Foxn1(nu), mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, lacking B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail, and condylomas of the vaginal lining which could be induced by separate scarification or simultaneous scarification of MmuPV1 at all four sites. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Although trichoepitheliomas are benign, aggressive tumors, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were highly dysregulated.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, United States of America.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Stearns
authors.affiliation: James Graham Brown Cancer Center (JGBCC), School of Medicine, University of Louisville, Louisville, KY, United States of America.
authors.forename: Joongho
authors.initials: J
authors.lastname: Joh
authors.affiliation: James Graham Brown Cancer Center (JGBCC), School of Medicine, University of Louisville, Louisville, KY, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Proctor
authors.affiliation: Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Ingle
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, United States of America.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Silva
authors.affiliation: Dept. Dermatology and Genetics/Developmental Biology, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Soheil S
authors.initials: SS
authors.lastname: Dadras
authors.affiliation: James Graham Brown Cancer Center (JGBCC), School of Medicine, University of Louisville, Louisville, KY, United States of America.
authors.forename: A Bennett
authors.initials: AB
authors.lastname: Jenson
authors.affiliation: James Graham Brown Cancer Center (JGBCC), School of Medicine, University of Louisville, Louisville, KY, United States of America.
authors.forename: Shin-je
authors.initials: SJ
authors.lastname: Ghim
mesh_terms: D000368:Aged; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D051747:DNA-Activated Protein Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010212:Papilloma / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity*; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C090140:Whn protein; C064658:RAG-1 protein; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse