The vertical transmission of HIV from mother to infant requires passage through the placenta or the newborn skin/mucous membrane surface, both of which are remarkably effective in protecting the fetus/infant in the majority of cases. Results from a variety of transmission settings (simian model, adult hetero- and homo-sexual, and vertical) support a common theme -the viral phenotype/genotype preferentially transmitted and/or amplified is generally homogenous, monocyte/macrophage-tropic, non-syncytium- inducing, with relatively slow growth characteristics. It is hypothesized that initial infection and dissemination events both within the placenta and the fetus/newborn are hosted and coordinated by trophoblasts and monocyte/macrophages with later viral evolution and recruitment of additional cell types. Early viral replication events and selection pressures together with the host immune response are hypothesized to be predictive of ultimate clinical course. This proposal endeavors to establish the phenotypic (cell culture assays), genotypic (DNA sequencing), and quantitative (PCR-based assays) properties of mv in a cohort of infected newborns and to monitor the characteristics of viral evolution through the first year of life. This will be coordinated with the evaluation of very early, non-specific immune response to infection - interferon alpha production as a marker of monocyte/macrophage and dendritic cell activation, and NK cell activity. Finally, an in vitro mucosal model will be utilized to study trans-mucosal transmission variables, focusing on both epithelial cells and cells of immune origin. Careful analysis of existing and future samples from a perinatal HIV transmission cohort is anticipated to provide insights into HIV transmission, prevention approaches, early viral pathogenesis and therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI039106-03
Application #
2517314
Study Section
Special Emphasis Panel (SRC (64))
Project Start
1995-09-30
Project End
2000-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Pediatrics
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107