title: The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/γcnull (NOG) mice.
abstract: BACKGROUND
  Human T-cell leukemia virus type 1 (HTLV-1) causes both neoplastic and inflammatory diseases, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Because these life-threatening and disabling diseases are not yet curable, it is important to prevent new HTLV-1 infections.
  
  
  RESULTS
  In this study, we have established a simple humanized mouse model of HTLV-1 infection for evaluating prophylactic and therapeutic interventions. In this model, HTLV-1-negative normal human peripheral blood mononuclear cells (PBMCs) are transplanted directly into the spleens of severely immunodeficient NOD-SCID/γcnull (NOG) mice, together with mitomycin-treated HTLV-1-producing T cells. Using this model, we tested the efficacy of monoclonal antibodies (mAbs) specific to HTLV-1 as well as human IgG isolated from HAM/TSP patients (HAM-IgG) in preventing HTLV-1-infection. One hour before and 24 h after transplantation of the human cells, each antibody sample was inoculated intraperitoneally. On day 14, human PBMCs isolated from the mouse spleens were tested for HTLV-1 infection. Whereas fresh CD4-positive and CD8-positive T cells isolated from untreated mice or mice treated with isotype control mAb, HTLV-1 non-neutralizing mAbs to envelope gp46, gag p19, and normal human IgG were all infected with HTLV-1; the mice treated with either HTLV-1 neutralizing anti-gp46 mAb or HAM-IgG did not become infected.
  
  
  CONCLUSIONS
  Our data indicate that the neutralizing function of the antibody, but not the antigen specificity, is essential for preventing the in vivo transmission of HTLV-1. The present animal model will also be useful for the in vivo evaluation of the efficacy of candidate molecules to be used as prophylactic and therapeutic intervention against HTLV-1 infection.
authors.forename: Mineki
authors.initials: M
authors.lastname: Saito
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Akira
authors.initials: A
authors.lastname: Kodama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology; D015490:HTLV-I Infections / Q000517:prevention & control* / Q000635:transmission; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015493:Paraparesis, Tropical Spastic / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology; D013601:T-Lymphocytes / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I