Clonal proliferation of HTLV-1-infected cells is associated with spontaneous malignant tumor formation in mice.
Adult T-cell leukemia/lymphoma (ATL) is characterized by monoclonal proliferation of tumor cells that harbor integrated human T-cell leukemia virus type-1 (HTLV-1). These malignant cells accumulate in various organs including the liver, spleen and skin in addition to blood and lymph nodes. Although there have been several reports of animal models of HTLV-1 infection in which proviral distribution has been examined, clonal expansion of the experimentally infected host cells has not been extensively analyzed. Here we provide experimental evidence that clonal proliferation of the infected host cells occurs in the spleen for more than one year. During a 15 month period of persistent infection, two out of ten mice developed spontaneous tumors. Although the tumors were not ATL-like, cells exhibiting mono- or oligoclonal proliferation and having the same site of HTLV-1 integration were identified in tumor tissues as well as in the spleen. Quantitative analysis of the cells belonging to each cell clone suggested that these proliferating cell clones were associated with the tumors and that spontaneous tumor tissues might provide a suitable microenvironment for proliferation and accumulation of infected cell clones at the late stage of infection.
Tanaka
Masakazu
M
Graduate School of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan.
Nitta
Takayuki
T
Yoshida
Toshinori
T
Konishi
Tomoko
T
Kawazu
Yusuke
Y
Fujisawa
Jun-ichi
J
Miwa
Masanao
M
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D002999:Clone Cells; D015490:HTLV-I Infections / Q000473:pathology / Q000821:virology*; D051642:Histiocytoma / Q000473:pathology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology / Q000821:virology; D008080:Liposarcoma / Q000473:pathology / Q000821:virology; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000473:pathology / Q000821:virology*; D012983:Soft Tissue Neoplasms / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000473:pathology / Q000821:virology*; D013160:Splenic Neoplasms / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration