期刊
CLINICAL AND VACCINE IMMUNOLOGY
卷 14, 期 4, 页码 391-396出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/CVI.00403-06
关键词
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资金
- NCI NIH HHS [P30 CA016042] Funding Source: Medline
- NIAID NIH HHS [R01 AI052002, R21 AI052002, AI052002, P30 AI028697, AI39975, R01 AI039975, AI28697] Funding Source: Medline
The goal of this study was to develop a small-animal model to study human immunodeficiency virus type 1 (HIV-1) pathogenesis in blood and primary and secondary lymphoid organs. Rag2(-/-)gamma(-/-)(c) mice that are neonatally injected with human CD34(+) cells develop a functional human immune system (HIS), with human hematopoietic cells being found in the thymuses, peripheral blood, spleens, and bone marrow of the animals (hereafter these animals are referred to as HIS-Rag2(-/-)gamma(-/-)(c) mice). HIS-Rag2(-/-)gamma(-/-)(c) mice were infected with small amounts of CCR5-tropic HIV-1. Viral replication and immunophenotypic changes in the human cells in peripheral blood and lymphoid organs were examined. The productive infection of human cells in peripheral blood, thymus and spleen tissue, and bone marrow was detected. Ratios of CD4(+) T cells to CD8(+) T cells in the infected animals declined. Although no specific anti-HIV-1 immune responses were detected, inummoglobulin M (IgM) and IgG antibodies to an unidentified fetal calf serum protein present in the virus reparation were found in the inoculated animals. Thus, we have shown that the HIS-Rag2(-/-)gamma(-/-)(c) mouse model can be used for infection with low doses of CCR5-tropic HIV-1, which is most commonly transmitted during primary infections. HIS-Rag2(-/-)gamma(-/-)(c) mice can serve as a small-animal model for investigating HIV-1 pathogenesis and testing potential HIV-1 therapies, and studies with this model may replace some long and costly studies with nonhuman primates.
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