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Complete prevention of HTLV-1 infection in humanized mice (hu-PBL SCID) by a neutralizing monoclonal antibody to envelope gp46

Human T-cell leukemia virus type 1 (HTLV-1) causes both neoplastic and inflammatory diseases: adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since these disabling and/or life threatening diseases are not yet curable, it is important to prevent new infections. In this study, we have established a simple humanized mouse model of HTLV-1 infection for evaluating therapeutic and immunomodulatory interventions. Using this model, we tested the effect of HTLV-1 specific neutralizing antibodies. HTLV-1-negative normal human peripheral blood mononuclear cells (PBMCs) were transplanted directly into the spleens of severely immunodeficient mice (NOD/SCID/γCnull: NOG) together with the mitomycin-treated HTLV-1 producing T cells (ILT-M1). Before (one hour) and after (24 hours) transplantation of human PBMCs, monoclonal antibodies against HTLV-1 as well as human IgG isolated from both HTLV-1 infected and non-infected individuals were inoculated intraperitonealy. On day 14, human PBMCs were isolated from mouse spleen, and tested for HTLV-1 infection by real time PCR and flow cytometry. Similar to the naturally HTLV-1 infected PBMCs, both CD4+ and CD8+ T cells isolated from untreated or isotype antibody treated mice were found to be HTLV-1 infected, and the CD8+ T cells harbored HTLV-1 to a lesser extent. Also, HTLV-1 Tax expression was negative in isolated human PBMCs but became positive after 16 hours of culture. Although non-neutralizing monoclonal antibodies to gp46, monoclonal antibody to gag p19, and normal human IgG did not block the infection, neutralizing monoclonal antibody to gp46 and human anti-HTLV-1 IgG completely blocked the infection. Our findings provide a new strategy for preventing initial HTLV-1 infection and blocking further spread in vivo. The potential mechanisms involved in the antibody effect will also be discussed.

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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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Saito, M., Tanaka, R., Kodama, A. et al. Complete prevention of HTLV-1 infection in humanized mice (hu-PBL SCID) by a neutralizing monoclonal antibody to envelope gp46. Retrovirology 11 (Suppl 1), O9 (2014).

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