Cvetkovich T A, Lazar E, Blumberg B M, Saito Y, Eskin T A, Reichman R, Baram D A, del Cerro C, Gendelman H E, del Cerro M
Department of Pediatrics, University of Rochester, Rochester, NY 14642.
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5162-6. doi: 10.1073/pnas.89.11.5162.
Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.
1型人类免疫缺陷病毒（HIV-1）感染对其人类宿主具有高度特异性。为了研究HIV-1对人类神经系统的感染，我们建立了一种小动物模型，即将孕中期（11至17.5周）的人类胎儿脑或神经视网膜移植到免疫抑制成年大鼠的眼前房。人类异种移植物形成血管，形成血脑屏障，并分化形成神经元和神经胶质细胞。这些异种移植物被无细胞HIV-1或感染HIV-1的人类单核细胞感染。聚合酶链反应分析显示，暴露于HIV-1病毒体的异种移植组织的DNA中存在HIV-1序列，原位杂交表明HIV-1 mRNA定位于巨噬细胞和多核巨细胞中。仅在含有感染HIV-1的人类单核细胞的神经异种移植物中观察到病理损伤，这支持了这些细胞介导神经毒性的假说。这种小动物模型可以研究HIV-1感染对发育中的人类胎儿神经组织的直接和间接影响，并且在评估抗病毒疗法方面应该是有用的，这些疗法最终必须针对脑部的HIV-1感染。
