Hiv-1 infection of human fetal thymocytes

Kathryn E. Tanaka, William C. Hatch, Yvonne Kress, Ruy Soeiro, Theresa Calvelli, William K. Rashbaum, Arye Rubinstein, William D. Lyman

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Summary: 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 >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 (HI V-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.

Original languageEnglish (US)
Pages (from-to)94-100
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume5
Issue number1
StatePublished - Jan 1992

Keywords

  • Development
  • HIV-1
  • Human fetus
  • Immune regulation
  • Thymocytes

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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