The recent increase in HIV-1 infected women of child- bearing age in the United States has resulted in a rising incidence of AIDS in pediatric populations. This maternal-neonatal transmission of HIV-1 from infected mother to child is the major source of infection in neonates. However, 70-85% of all infants born of HIV-1 seropositive mothers do not become infected with HIV-1. The reason for this protection from infection is not known. The goal of this project is to evaluate the role of maternal HIV-1 antibodies in the transmission outcome of HIV-1 in infants. The genetic variations between the mother and child isolates and their relative sensitivity to serum antibodies will be considered. A comparative study will be conducted of HIV-1 isolates obtained from seropositive mothers of uninfected neonates, from seropositive mothers of infected infants and from the infected infants themselves. The susceptibility of the viral isolates to neutralization or enhancement by the autologous sera from mothers and infants will be determined in reference to protection or promotion of the infection in infants. Specific regions in the viral envelope at the principal neutralization domain and neighboring domains in the third hypervariable segment (V3), possibly mediating the neutralization or enhancement will be identified. The use of peptides for these PPP regions as immunological probes to predict the transmission outcome will be assessed. The genetic variation at the V3 region(s) in both mother and infant isolates will be determined by sequencing the polymerase chain reaction (PCR) product of the V3 loop. The site(s) that correlate with HIV infection or protection of neonates will be evaluated for usefulness as a genetic marker to predict the clinical outcome in infants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032446-04
Application #
2067336
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1991-09-30
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kliks, S; Contag, C H; Corliss, H et al. (2000) Genetic analysis of viral variants selected in transmission of human immunodeficiency viruses to newborns. AIDS Res Hum Retroviruses 16:1223-33
Kliks, S C; Wara, D W; Landers, D V et al. (1994) Features of HIV-1 that could influence maternal-child transmission. JAMA 272:467-74