Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds
Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds
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DOI：
10.1128/aac.40.3.755
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发表时间：
1996-03-01
影响因子：
4.9
通讯作者：
McCune, JM
中科院分区：
文献类型：
--
作者：
Rabin, L;Hincenbergs, M;McCune, JM
我们已经制定了标准化的程序和实践，用于用人类免疫缺陷病毒1型感染SCID-hu Thy/Liv小鼠，用于预防性给予抗病毒化合物和评价体内抗病毒效果。终点分析包括通过细胞内p24酶联免疫吸附试验定量病毒载量，DNA PCR检测前病毒基因组的存在，流式细胞术测量CD 4（+）和CD 8（+）细胞的代表性，以及共培养分离病毒。在该模型中的有效性试验证明了与核苷类似物齐多夫定和双脱氧肌苷和非核苷逆转录酶抑制剂奈韦拉平。这种小动物模型在临床前优先考虑常见化学类别中的先导化合物、评价替代体内给药方案以及确定适当的体内联合治疗中特别有用。
We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4(+) and CD8(+) cells, and cocultivation for-the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo.