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Journal of Virology, December 2007, p. 13259-13264, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01353-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Humanized NOD/SCID/IL2R^null Mice Transplanted with Hematopoietic Stem Cells under Nonmyeloablative Conditions Show Prolonged Life Spans and Allow Detailed Analysis of Human Immunodeficiency Virus Type 1 Pathogenesis

Department of Virology, Division of Medical Science, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan,¹ Open Research Center for Genome and Infectious Disease Control, Nihon University School of Medicine, 30-1 Oyaguchikami-chou, Itabashi-ku, Tokyo 173-8610, Japan,² AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan,³ Department of Infectious Diseases, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 154-8567, Japan,⁴ Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan,⁵ Central Institute for Experimental Animals, 1430 Nogawa, Miyamae-ku, Kawasaki, Kanagawa 216-0001, Japan,⁶ Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1 Oyaguchikami-chou, Itabashi-ku, Tokyo 173-8610, Japan⁷

Received 21 June 2007/ Accepted 3 September 2007

In a previous study, we demonstrated that humanized NOD/SCID/IL2R^null (hNOG) mice constructed with human hematopoietic stem cells (HSCs) allow efficient human immunodeficiency virus type 1 (HIV-1) infection. However, HIV-1 infection could be monitored for only 43 days in the animals due to their short life spans. By transplanting HSCs without any myeloablation methods, the mice successfully survived longer than 300 days with stable engraftment of human cells. The mice showed high viremia state for more than the 3 months examined, with systemic HIV-1 infection and gradual decrease of CD4⁺ T cells analogous to that in humans. These capacities of the hNOG mice are very attractive for modeling mechanisms of AIDS progression and therapeutic strategy.

Published ahead of print on 19 September 2007.