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Carrier model of HTLV-1 infection in humanized NOG mice

HTLV-1 infection leads to adult T-cell leukemia (ATL) after long latent infection period. We have established an HTLV-1-infected humanized NOG mouse model to analyze the mechanism of ATL development. Humanized mice were inoculated with Jurkat-based HTLV-1 producing cells, JEX, into peritoneal cavity to infect human T-cells with HTLV-1. Infected T-cells proliferated vigorously in infected mice and the mice died of ALT-like lymphoproliferative disorder with attenuated HTLV-1 specific immunoresponses within two to three months of infection. In contrast, when HTLV-1 producing cells were inoculated orally, infection of human T-cells was established but the proviral loads (PVL) was kept constant in small amount (0.2-9.5 copies / 100 PBMCs) without any pathological feature, even after 18 weeks post infection. The amount of antibody against HTLV-1 in the plasma of orally infected mice was equivalent to that of intraperitoneally infected mice at 2-6 weeks post infection. The titer of antibody was maintained throughout lifetime in orally infected mice but not in intraperitoneally infected mice. Furthermore, depletion of CD8 T-cells from orally infected mice by injecting anti-CD8 antibody resulted in transient increase of PVL in PBMCs, indicating the involvement of cytotoxic T-cells in the control of PVL in these mice. Thus, orally infected humanized NOG mice should provide a model system of HTLV-1 carrier to examine factors involved in the development of ATL from carrier state and play a significant role in evaluating preventive vaccine candidates and antiretroviral drugs for HTLV-1 infection.

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Correspondence to Kenta Tezuka.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Tezuka, K., Tei, M., Ueno, T. et al. Carrier model of HTLV-1 infection in humanized NOG mice. Retrovirology 11 (Suppl 1), P42 (2014).

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