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. 1992 Jun 1;89(11):5162–5166. doi: 10.1073/pnas.89.11.5162

Human immunodeficiency virus type 1 infection of neural xenografts.

T A Cvetkovich 1, E Lazar 1, B M Blumberg 1, Y Saito 1, T A Eskin 1, R Reichman 1, D A Baram 1, C del Cerro 1, H E Gendelman 1, M del Cerro 1, et al.
PMCID: PMC49249  PMID: 1594627

Abstract

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.

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