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Clin. Vaccine Immunol. doi:10.1128/CVI.00403-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Human immune system (HIS) RAG^-/-c^-/- mouse, a novel chimeric mouse model for HIV-1 infection

Departments of Medicine, Microbiology, Immunology, and Molecular Genetics, Pediatrics, UCLA AIDS Institute, Jonsson Comprehensive Cancer Center, David E. Geffen School of Medicine at UCLA, Los Angeles California; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. Email: uittenbo{at}ucla.edu.

	Abstract

The goal of the study was to develop a small animal model to study HIV-1 pathogenesis in blood and primary and secondary lymphoid organs. In our recently described "human immune system" RAG2^-/-_c^-/- (HIS-RAG2^-/-_c^-/-) mice, that are neonatally reconstituted with human CD34⁺ cells, human hematopoietic cells are found in the reconstituted animals in the murine thymus, peripheral blood, spleen and bone marrow. HIS-RAG2^-/-_c^-/- mice were infected with low amounts of CCR5-tropic HIV-1. Viral replication and immunophenotypic changes in the human cells were examined in peripheral blood and lymphoid organs. Productive infection of human cells was detected in peripheral blood, thymus spleen and bone marrow. Ratios of CD4⁺/CD8⁺ T-cells declined in the infected animals. Although no specific anti-HIV-1 immune responses were detected, IgM and IgG antibodies to an unidentified fetal calf serum protein present in the virus preparation were found in the inoculated animals. Thus we have shown that the HIS-RAG2^-/-_c^-/- mouse model can be infected with low doses of CCR5-tropic HIV-1, which is most commonly transmitted during primary infections. The HIS-RAG2^-/-_c^-/- mouse can serve as a small animal model for investigating HIV-1 pathogenesis and testing potential HIV-1 therapies and may replace some long and costly studies in non-human primates.