This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02010-06v1 81/6/2700    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gorantla, S. Articles by Poluektova, L. Search for Related Content PubMed PubMed Citation Articles by Gorantla, S. Articles by Poluektova, L.

Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2^–/–_c^–/– Mice

Center for Neurovirology and Neurodegenerative Disorders and Department of Pharmacology and Experimental Neuroscience and Departments of,¹ Internal Medicine,² Genetics, Cell Biology and Anatomy,³ Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska,⁴ Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska,⁵ Department of Microbiology and Immunology and James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York⁶

Received 14 September 2006/ Accepted 13 December 2006

The specificity of human immunodeficiency virus type 1 (HIV-1) for human cells precludes virus infection in most mammalian species and limits the utility of small animal models for studies of disease pathogenesis, therapy, and vaccine development. One way to overcome this limitation is by human cell xenotransplantation in immune-deficient mice. However, this has proved inadequate, as engraftment of human immune cells is limited (both functionally and quantitatively) following transplantation of mature human lymphocytes or fetal thymus/liver. To this end, a human immune system was generated from umbilical cord blood-derived CD34⁺ hematopoietic stem cells in BALB/c-Rag2^–/–_c^–/– mice. Intrapartum busulfan administration followed by irradiation of newborn pups resulted in uniform engraftment characterized by human T-cell development in thymus, B-cell maturation in bone marrow, lymph node development, immunoglobulin M (IgM)/IgG production, and humoral immune responses following ActHIB vaccination. Infection of reconstituted mice by CCR5-coreceptor utilizing HIV-1_ADA and subtype C 1157 viral strains elicited productive viral replication and lymphadenopathy in a dose-dependent fashion. We conclude that humanized BALB/c-Rag2^–/–_c^–/– mice represent a unique and valuable resource for HIV-1 pathobiology studies.

Published ahead of print on 20 December 2006.

This article has been cited by other articles:

• Watanabe, S., Ohta, S., Yajima, M., Terashima, K., Ito, M., Mugishima, H., Fujiwara, S., Shimizu, K., Honda, M., Shimizu, N., Yamamoto, N. (2007). Humanized NOD/SCID/IL2R{gamma}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. J. Virol. 81: 13259-13264 [Abstract] [Full Text]  
• Munk, C., Zielonka, J., Constabel, H., Kloke, B.-P., Rengstl, B., Battenberg, M., Bonci, F., Pistello, M., Lochelt, M., Cichutek, K. (2007). Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells. J. Virol. 81: 7048-7060 [Abstract] [Full Text]  
• An, D. S., Poon, B., Fang, R. H. T., Weijer, K., Blom, B., Spits, H., Chen, I. S. Y., Uittenbogaart, C. H. (2007). Use of a Novel Chimeric Mouse Model with a Functionally Active Human Immune System To Study Human Immunodeficiency Virus Type 1 Infection. CVI 14: 391-396 [Abstract] [Full Text]