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 E.
AU - Del Cerro, Manuel
AU - Epstein, Leon G.
PY - 1992
Y1 - 1992
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
C2 - 1594627
AN - SCOPUS:0026684171
SN - 0027-8424
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
IS - 11
ER -
