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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 (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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 20, 2006 Accepted August 12, 2006 hematopoietic stem cell-engrafted NOD/SCID/IL2Rnull mice develop human lymphoid system and induce long-lasting HIV-1 infection with specific humoral immune responses Satoru Watanabe, Kazuo Terashima, Shinrai Ohta, Shigeo Horibata, Misako Yajima, Yoko Shiozawa, Md. Zahidunnabi Dewan, Zhong Yu, Mamoru Ito, Tomohiro Morio, Norio Shimizu, Mitsuo Honda, and Naoki Yamamoto* Department of Virology, Tokyo Medical and Dental University, Tokyo, Japan Department of Molecular Virology, Tokyo Medical and Dental University AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan National Research Institute for Child Health and Development, Tokyo, Japan Tokyo Medical and Dental University/AIDS Research Center, Tokyo, Japan Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan Central Institute for Experimental Animals, Kanagawa, Japan Tokyo Medical and Dental University, Tokyo, Japan Department of Virology, Tokyo Medical and Dental University Tokyo Medical and Dental University, National Institute of Infectious Diseases, Tokyo, Japan * Corresponding author; email: nyama{at}nih.go.jp. 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 NOD/SCID/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 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, 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 spleen and bone marrow, and X4 virus-infected animals in 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 with 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?

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