オオダカ　トキフミ   ODAKA TOKIFUMI   大高　時文    所属   関西医科大学  微生物学講座    職種   助教
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	Reduction of human T-cell leukemia virus type-1 infection in mice lacking nuclear factor-kappaB-inducing kinase.
掲載誌名	正式名：Cancer Science 略　 称：Cancer Sci ISSNコード：13479032/13497006
巻・号・頁	99(5),pp.872-878
著者・共著者	Nitta T, Tanaka M, Sun B, Sugihara E, Kimura M, Kamada Y, Takahashi H, Hanai S, Jiang SW, Fujisawa J, Miwa M
発行年月	2008/05
概要	Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory disorders. Aberrant activation of nuclear factor-kappaB (NF-kappaB) has been linked to HTLV-1 pathogenesis and to various kinds of cancers, including adult T-cell leukemia. NF-kappaB-inducing kinase (NIK) is critical for non-canonical activation of NF-kappaB and for the development of lymphoid organs. HTLV-1 activates NF-kappaB by the non-canonical pathway, but examination of the role of NIK in proliferation of HTLV-1-infected cells in vivo has been hindered by lack of a suitable animal model. Alymphoplasia (aly/aly) mice bear a mutation of NIK, resulting in defects in the development of lymphoid organs and severe deficiencies in both humoral and cell-mediated immunity. In the present study we therefore used a mouse model of HTLV-1 infection with aly/aly mice. The number of HTLV-1-infected cells in the reservoir organs in aly/aly mice was significantly smaller than in the control group 1 month after infection. In addition, aly/aly mice did not maintain provirus for 1 year and antibodies against HTLV-1 were undetectable. These results demonstrate that the absence of functional NIK impairs primary HTLV-1 proliferation and abolishes the maintenance of provirus. Interestingly, clonal proliferation of HTLV-1-infected mouse cells was not detected in aly/aly mice, which is consistent with the lack of HTLV-1 persistence. These observations imply that the clonal proliferation of HTLV-1-infected cells in secondary lymphoid organs might be important for HTLV-1 persistence.
文献番号	18312467