Reduction of human T-cell leukemia virus type-1 infection in mice lacking nuclear factor-kappaB-inducing kinase.
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.
Nitta
Takayuki
T
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Tanaka
Masakazu
M
Sun
Binlian
B
Sugihara
Eiji
E
Kimura
Mako
M
Kamada
Yuhei
Y
Takahashi
Hideto
H
Hanai
Shuji
S
Jiang
Shi-Wen
SW
Fujisawa
Jun-ichi
J
Miwa
Masanao
M
D000818:Animals; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D015490:HTLV-I Infections / Q000201:enzymology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012367:RNA, Viral / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D017346:Protein Serine-Threonine Kinases; D012367:RNA, Viral; D000097782:NF-kappaB-Inducing Kinase