Jamieson B D, Zack J A
Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine and UCLA AIDS Institute, Los Angeles, California 90095-1678, USA.
J Virol. 1998 Aug;72(8):6520-6. doi: 10.1128/JVI.72.8.6520-6526.1998.
Our understanding of human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis is hampered by the inability to detect HIV-1 gene expression in infected viable cells. In this report, we describe two HIV-1 reporter constructs that are replication competent and cytopathic in vivo. These constructs contain DNA regions of two different lengths that bear the cDNA for the murine heat-stable antigen in the vpr region of a CXCR4-tropic virus. We used the SCID-hu mouse model and these reporter viruses to perform detailed kinetic studies of HIV-1 infection of human thymocytes in vivo. We document that the CD4(+)/CD8(+) thymocytes are the first to express virus and that this subset demonstrates the most rapid and extensive HIV-1-induced cell depletion. Following depletion of this subset, subsequent virus expression occurs predominantly in phenotypically CD4(-) cells, suggesting that CD4 down-regulation occurs in HIV-1-infected thymocytes in vivo. These results demonstrate the utility of these HIV-1 reporter constructs to monitor HIV pathogenesis in vitro and in vivo.
由于无法在受感染的活细胞中检测到HIV-1基因表达，我们对1型人类免疫缺陷病毒（HIV-1）诱导的发病机制的理解受到了阻碍。在本报告中，我们描述了两种在体内具有复制能力且具有细胞病变效应的HIV-1报告基因构建体。这些构建体包含两个不同长度的DNA区域，它们在趋化因子受体CXCR4型病毒的vpr区域携带鼠热稳定抗原的cDNA。我们使用SCID-hu小鼠模型和这些报告病毒对体内人类胸腺细胞的HIV-1感染进行了详细的动力学研究。我们证明CD4(+)/CD8(+)胸腺细胞是最先表达病毒的细胞，并且该亚群表现出最迅速和广泛的HIV-1诱导的细胞耗竭。在该亚群耗竭后，随后的病毒表达主要发生在表型为CD4(-)的细胞中，这表明在体内感染HIV-1的胸腺细胞中发生了CD4下调。这些结果证明了这些HIV-1报告基因构建体在体外和体内监测HIV发病机制的实用性。
