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 Eliot Gendelman, Manuel Del Cerro, Leon G. Epstein

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 - Jan 1 1992

Fingerprint

Virus Diseases
Heterografts
HIV-1
Monocytes
Animal Models
Brain
Anterior Chamber
Second Pregnancy Trimester
Giant Cells
Blood-Brain Barrier
Neuroglia
Virion
Nervous System
In Situ Hybridization
Antiviral Agents
Retina
Fetus
Macrophages
Neurons
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Cvetkovich, T. A., Lazar, E., Blumberg, B. M., Saito, Y., Eskin, T. A., Reichman, R., ... 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

Human immunodeficiency virus type 1 infection of neural xenografts. / Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; Del Cerro, Coca; Gendelman, Howard Eliot; Del Cerro, Manuel; Epstein, Leon G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 11, 01.01.1992, p. 5162-5166.

Research output: Contribution to journalArticle

Cvetkovich, TA, Lazar, E, Blumberg, BM, Saito, Y, Eskin, TA, Reichman, R, Baram, DA, Del Cerro, C, Gendelman, HE, Del Cerro, M & Epstein, LG 1992, 'Human immunodeficiency virus type 1 infection of neural xenografts', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 11, pp. 5162-5166. https://doi.org/10.1073/pnas.89.11.5162
Cvetkovich, Therese A. ; Lazar, Eliot ; Blumberg, Benjamin M. ; Saito, Yoshihiro ; Eskin, Thomas A. ; Reichman, Richard ; Baram, David A. ; Del Cerro, Coca ; Gendelman, Howard Eliot ; Del Cerro, Manuel ; Epstein, Leon G. / Human immunodeficiency virus type 1 infection of neural xenografts. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 11. pp. 5162-5166.
@article{c7c54cefb0244b50b47673ccd10b3bb8,
title = "Human immunodeficiency virus type 1 infection of neural xenografts",
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.",
keywords = "AIDS, Central nervous system, Fetal brain, Monocyte macrophage",
author = "Cvetkovich, {Therese A.} and Eliot Lazar and Blumberg, {Benjamin M.} and Yoshihiro Saito and Eskin, {Thomas A.} and Richard Reichman and Baram, {David A.} and {Del Cerro}, Coca and Gendelman, {Howard Eliot} and {Del Cerro}, Manuel and Epstein, {Leon G.}",
year = "1992",
month = "1",
day = "1",
doi = "10.1073/pnas.89.11.5162",
language = "English (US)",
volume = "89",
pages = "5162--5166",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "11",

}

TY - JOUR

T1 - Human immunodeficiency virus type 1 infection of neural xenografts

AU - Cvetkovich, Therese A.

AU - Lazar, Eliot

AU - Blumberg, Benjamin M.

AU - Saito, Yoshihiro

AU - Eskin, Thomas A.

AU - Reichman, Richard

AU - Baram, David A.

AU - Del Cerro, Coca

AU - Gendelman, Howard Eliot

AU - Del Cerro, Manuel

AU - Epstein, Leon G.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - 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.

AB - 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.

KW - AIDS

KW - Central nervous system

KW - Fetal brain

KW - Monocyte macrophage

UR - http://www.scopus.com/inward/record.url?scp=0026684171&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026684171&partnerID=8YFLogxK

U2 - 10.1073/pnas.89.11.5162

DO - 10.1073/pnas.89.11.5162

M3 - Article

VL - 89

SP - 5162

EP - 5166

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 11

ER -