MOTHER/CHILD HIV-1 ISOLATES AND SEQUENCES

Project: Research project

Project Details

Description

We propose to address 3 central issues in vertical transmission of HIV-1
infection from mother to child. These issues are: l) occurrence of
vertical transmission of HIV-1 from 25-30% of infected pregnant women to
their offspring but lack of transmission to the majority of these
offspring; 2) the widely variable pace of HIV-1 -related disease
progression in children; and 3) timing and route of transmission from
mother to child. We aim to investigate the roles of HIV-1 nucleotide
sequence diversity and neutralization of HIV-1 quasispecies in vertical
transmission and disease progression and to study the timing and route of
vertical transmission from mother to child. We plan to analyze serial blood specimens from our established cohort of
infected pregnant women and mother-child pairs in NY and NJ who reflect
the racial and ethnic distribution of AIDS in the U.S. We aim to: 1)
Determine the nucleotide sequences of portions of the HIV-1 envelope (V1,
V3, V4, C4) by using PCR amplification of uncultivated peripheral blood
mononuclear cells (PBMCs) and plasma. We will measure the degree of
diversity present within specimens at each time point and determine the
change in diversity. over time; 2) Utilize sequence data obtained from
pregnant women and their infected offspring at different time points and
from different fluid compartments as well as virologic, immunologic, and
clinical data to investigate the timing and route of vertical
transmission; 3) Quantitate HIV-1 cultured from PBMCs and plasma by
limiting dilution and determine the relationship between the degree of
diversity and viral load within single patient specimens; 4) Study
neutralization of HIV-1 quasispecies by assaying sera from mother and
child. We shall examine neutralization of quasispecies in virus cultivated
from mother and child and shall determine the sequence of portions of env
(V1, V3, V4, C4) of viruses which are neutralized and those that escape
neutralization; and 5) Correlate molecular, viral, and neutralization data
with the occurrence of vertical transmission and pace of disease
progression in children.
StatusFinished
Effective start/end date9/30/934/30/99

Funding

  • National Institutes of Health
  • National Institutes of Health: $165,093.00
  • National Institutes of Health: $133,636.00
  • National Institutes of Health

ASJC

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

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