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Blood, 1 January 2007, Vol. 109, No. 1, pp. 212-218. Prepublished online as a Blood First Edition Paper on September 5, 2006; DOI 10.1182/blood-2006-04-017681. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-017681v1 109/1/212    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Watanabe, S. Articles by Yamamoto, N. Search for Related Content PubMed PubMed Citation Articles by Watanabe, S. Articles by Yamamoto, N. Related Collections Hematopoiesis and Stem Cells Immunobiology Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Hematopoietic stem cell–engrafted NOD/SCID/IL2Rnull mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses Satoru Watanabe1, Kazuo Terashima2, Shinrai Ohta3, Shigeo Horibata3, Misako Yajima4, Yoko Shiozawa1, M. Zahidunnabi Dewan2,3, Zhong Yu2, Mamoru Ito5, Tomohiro Morio6, Norio Shimizu1,, Mitsuo Honda3,, and Naoki Yamamoto2,3, 1 Department of Virology, Division of Medical Science, Medical Research Institute, Tokyo Medical and Dental University, Japan; 2 Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan; 3 AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; 4 Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo, Japan; 5 Central Institute for Experimental Animals, Kanagawa, Japan; and 6 Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan Critical to the development of an effective HIV/AIDS model is the production of an animal model that reproduces long-lasting active replication of HIV-1 followed by elicitation of virus-specific immune responses. In this study, we constructed humanized nonobese diabetic/severe combined immunodeficiency (NOD/SCID)/interleukin-2 receptor -chain knockout (IL2Rnull) (hNOG) mice by transplanting human cord blood–derived hematopoietic stem cells that eventually developed into human B cells, T cells, and other monocytes/macrophages and 4 dendritic cells associated with the generation of lymphoid follicle–like structures in lymphoid tissues. Expressions of CXCR4 and CCR5 antigens were recognized on CD4+ cells in peripheral blood, the spleen, and bone marrow, while CCR5 was not detected on thymic CD4+ T cells. The hNOG mice showed marked, long-lasting viremia after infection with both CCR5- and CXCR4-tropic HIV-1 isolates for more than the 40 days examined, with R5 virus–infected animals showing high levels of HIV-DNA copies in the spleen and bone marrow, and X4 virus–infected animals showing high levels of HIV-DNA copies in the thymus and spleen. Furthermore, we detected both anti–HIV-1 Env gp120– and Gag p24–specific antibodies in animals showing a high rate of viral infection. Thus, the hNOG mice mirror human systemic HIV infection by developing specific antibodies, suggesting that they may have potential as an HIV/AIDS animal model for the study of HIV pathogenesis and immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kwant-Mitchell, A. A. Ashkar, and K. L. Rosenthal Mucosal Innate and Adaptive Immune Responses against Herpes Simplex Virus Type 2 in a Humanized Mouse Model J. Virol., October 15, 2009; 83(20): 10664 - 10676. [Abstract] [Full Text] [PDF] J. Mota and R. Rico-Hesse Humanized Mice Show Clinical Signs of Dengue Fever according to Infecting Virus Genotype J. Virol., September 1, 2009; 83(17): 8638 - 8645. [Abstract] [Full Text] [PDF] J. Unsinger, J. S. McDonough, L. D. Shultz, T. A. Ferguson, and R. S. 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