Human immunodeficiency virus type 1 infection of neural xenografts.
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.
Cvetkovich
T A
TA
Department of Pediatrics, University of Rochester, Rochester, NY 14642.
Lazar
E
E
Blumberg
B M
BM
Saito
Y
Y
Eskin
T A
TA
Reichman
R
R
Baram
D A
DA
del Cerro
C
C
Gendelman
H E
HE
del Cerro
M
M
D015526:AIDS Dementia Complex / Q000382:microbiology*; D000818:Animals; D000867:Anterior Chamber; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D004279:DNA, Viral / Q000032:analysis; D005333:Fetus; D005814:Genes, Viral; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D051381:Rats; D012160:Retina; D014183:Transplantation, Heterologous; D015678:Viral Structural Proteins / Q000235:genetics
D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D015678:Viral Structural Proteins