Project: Research project

Project Details


Evidence for the transmission of HIV from mother to fetus via the
placenta has been documented but the mechanism of transmission is
unknown. The overall aim of this proposal is to determine the cellular
and molecular mechanisms involved in the placental transport of HIV from
maternal blood to the fetus. This objective will be pursued by taking
advantage of our ability to obtain pure population of human trophoblast
cells and our ability to demonstrate cell-mediated infection of these
cells in vitro. Placental syncytiotrophoblast is in direct contact with
maternal blood and virus must cross this epithelium before reaching
stromal cells, endothelial cells and, eventually, the fetal bloodstream.
The first specific aim will focus on characterizing the role of
lymphocytic/monocytic cells in the cell-mediated infection of
syncytiotrophoblast. We will use immunocytochemical and transmission
and scanning electron microscopic techniques to study the kinetics of
the cell-cell interaction and the infection process. The cellular
pathway by which HIV enters the cells will be defined. The possibility
that cytokines or other factors released by lymphocytic/monocytic cells
play a role in the cell mediated infection process will be studied.
Other experiments will establish the nature of the adhesion molecules
involved in cell-cell binding and analyze the role of antibody and CD4
in the infection process. In the second specific we aim will attempt to
determine whether the interaction of HIV with syncytiotrophoblast varies
as a function of gestational age by characterizing the nature of HIV
infection of cells obtained from first and second trimester placentas.
In the third specific aim we will determine whether anti-viral
dideoxynucleosides prevent HIV infection of placental cells and whether
cell function is compromised. In the last specific aim we will focus on
placental macrophages, fibroblasts and endothelial cells. As well as
characterizing viral internalization and release we will examine in
vitro infected cells for alterations in the secretion of cytokines and
growth factors. Information gained should be useful in designing
strategies to prevent HIV transmission.
Effective start/end date9/30/917/31/96


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Immunology and Microbiology(all)


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