title: Monoclonally integrated HTLV type 1 in epithelial cancers from rabbits infected with an HTLV type 1 molecular clone.
abstract: In addition to T cell leukemias and lymphomas, human T cell leukemia virus type 1 (HTLV-1) infection has been associated with nonhematologic malignancies and described as the cause of one case of small-cell lung carcinoma. Infected primary epithelial cells have been isolated from sweat gland and oral mucosae of HTLV-1-infected human patients. In the present study, epithelial neoplasms developed in two rabbits experimentally infected with a molecular clone of HTLV-1 (strain K30p). Serologic detection of anti-HTLV-1 and isolation of virus from blood lymphocytes at multiple time points postinjection established a course of chronic asymptomatic infection in both. One rabbit, infected for 5.5 years after intramuscular injection of HTLV-1 DNA, developed a thymoma having features of medullary differentiation. HTLV-1 provirus was detected in both thymocytes and neoplastic epithelium isolated discretely from the thymoma by laser capture microdissection. These findings provide the first experimental evidence of HTLV-1 disease after infection by HTLV-1 DNA injection. Endometrial adenocarcinoma occurred in a second rabbit 2.5 years after its inoculation with cell-associated virus. In this second case, an epithelial cell line derived ex vivo from a metastatic lesion produced virus in culture. In tumors from each of the two rabbits, the neoplastic epithelium was infected and harbored monoclonally integrated HTLV-1 provirus. Although monoclonal provirus integration alone does not establish retroviral cause of carcinogenesis unequivocally, these and other accumulating data indicate that there may be a role for HTLV-1 in diseases associated with infection of epithelia, including some epithelial cancers.
authors.affiliation: Molecular and Cellular Immunogenetics Research Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
authors.forename: Tong Mao
authors.initials: TM
authors.lastname: Zhao
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bryant
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kindt
authors.forename: R Mark
authors.initials: RM
authors.lastname: Simpson
mesh_terms: D000818:Animals; D015490:HTLV-I Infections / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D009374:Neoplasms, Experimental / Q000648:ultrastructure / Q000821:virology*; D011817:Rabbits; D016662:Virus Integration