Human immunodeficiency virus type 1 infection of neural xenografts

Therese A. Cvetkovich, Eliot Lazar, Benjamin M. Blumberg, Yoshihiro Saito, Thomas A. Eskin, Richard Reichman, David A. Baram, Coca Del Cerro, Howard E. Gendelman, Manuel Del Cerro, Leon G. Epstein

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5162-5166
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number11
DOIs
StatePublished - 1992

Keywords

  • AIDS
  • Central nervous system
  • Fetal brain
  • Monocyte macrophage

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Human immunodeficiency virus type 1 infection of neural xenografts'. Together they form a unique fingerprint.

  • Cite this

    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., & Epstein, L. G. (1992). Human immunodeficiency virus type 1 infection of neural xenografts. Proceedings of the National Academy of Sciences of the United States of America, 89(11), 5162-5166. https://doi.org/10.1073/pnas.89.11.5162