HIV-1 infection of human fetal thymocytes.
Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions.
Tanaka
K E
KE
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Hatch
W C
WC
Kress
Y
Y
Soeiro
R
R
Calvelli
T
T
Rashbaum
W K
WK
Rubinstein
A
A
Lyman
W D
WD
D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D005865:Gestational Age; D015726:Giant Cells; D015497:HIV-1 / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008854:Microscopy, Electron; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D013601:T-Lymphocytes / Q000382:microbiology* / Q000648:ultrastructure; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000648:ultrastructure; D014771:Virion / Q000502:physiology* / Q000648:ultrastructure
D004279:DNA, Viral