Reduction of human T-cell leukemia virus type-1 infection in mice lacking nuclear factor-κB-inducing kinase

Takayuki Nitta, Masakazu Tanaka, Binlian Sun, Eiji Sugihara, Mako Kimura, Yuhei Kamada, Hideto Takahashi, Shuji Hanai, Shi Wen Jiang, Jun Ichi Fujisawa, Masanao Miwa

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10 Citations (Scopus)


Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory disorders. Aberrant activation of nuclear factor-κB (NF-kappa;B) has been linked to HTLV-1 pathogenesis and to various kinds of cancers, including adult T-cell leukemia. NF-kappa;B-inducing kinase (NIK) is critical for non-canonical activation of NF-kappa;B and for the development of lymphoid organs. HTLV-1 activates NF-kappa;B by the non-canonical pathway, but examination of the role of NIK in proliferation of HTLV-1-infected cells 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.

Original languageEnglish
Pages (from-to)872-878
Number of pages7
JournalCancer science
Issue number5
Publication statusPublished - 05-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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