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Journal of Virology, May 2003, p. 5286-5294, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5286-5294.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Rapid Tumor Formation of Human T-Cell Leukemia Virus Type 1-Infected Cell Lines in Novel NOD-SCID/{gamma}cnull Mice: Suppression by an Inhibitor against NF-{kappa}B

M. Zahidunnabi Dewan,1 Kazuo Terashima,1 Midori Taruishi,1 Hideki Hasegawa,2 Mamoru Ito,3 Yuetsu Tanaka,4 Naoki Mori,5 Tetsutaro Sata,2 Yoshio Koyanagi,6 Michiyuki Maeda,7 Yoko Kubuki,8 Akihiko Okayama,8 Masahiro Fujii,9 and Naoki Yamamoto1*

Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519,1 Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640,2 Central Institute for Experimental Animals, Kawasaki 216,3 Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science,4 Department of Virology, Faculty of Medicine, University of the Ryukyus, Okinawa 905-0215,5 Department of Virology, School of Medicine, Tohoku University, Sendai 980-8575,6 Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507,7 Department of Internal Medicine II, Miyazaki Medical College, Miyazaki 889-1601,8 Department of Virology, Niigata University School of Medicine, Niigata 951, Japan9

Received 16 August 2002/ Accepted 24 January 2003

We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/{gamma}cnull (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common {gamma}-chain after 2 weeks. In vivo NF-{kappa}B DNA binding activity of the ED-40515(-) cell line was higher and the NF-{kappa}B components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-{kappa}B inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.

* Corresponding author. Mailing address: Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Phone: 81-3-5803-5178. Fax: 81-3-5803-0124. E-mail: yamamoto.mmb{at}tmd.ac.jp.

Journal of Virology, May 2003, p. 5286-5294, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5286-5294.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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