The research contained in this application will focus on host factors that modulate HIV infection. Specifically, the application will concern the role of the human fetal thymus and placenta in in utero HIV infection and the unexpected consequence of early spontaneous abortions suggested by evidence gathered on Baylor grant R01 AI32466-04, """"""""Role of the Placenta in Transmission of HIV."""""""" The long-term objective of this research application is directed at answering critical questions of the importance of host factors in the early HIV immunopathogenesis in vertically-acquired HIV infection acquired in utero.
The specific aims are to: 1) explore the role of the thymus in early rejection of the HIV-infected fetus in first and second trimester spontaneous abortions in HIV-infected women, 2) determine the role that cytokines in the placenta play in fetal loss in HIV infection, and 3) compare the phenotypic/genotypic characteristics of HIV in the early trimester aborted HIV-infected fetus to those in the mother. The applicant proposes to explore the immune mechanisms of rejection of the fetus, possibly mediated by factors (inflammatory cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha) derived from the placenta or by the fetus as a consequence of HIV infection. The project will utilize an existing model of HIV infection, a fetal thymus organ culture (FTOC) system. This model system of HIV infection will allow the careful interpretation of the importance of timing of HIV infection and viral burden/viral strain in early fetal death. The methods to be used include: 1) recruitment of HIV-infected pregnant women in a Pediatric/Obstetrical Research Center; 2) pathological examination of fetal and maternal products of conception, including in situ hybridization studies; 3) denaturing gradient gel electrophoresis, single strand conformation polymorphism, gene sequencing, and T cell and macrophage/monocyte tropism studies of HIV strains recovered from fetus and mother; 4) measurement of mRNA and protein product of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha; and 5) HIV infection (and pathological consequences) in an FTOC system in vitro.
| Lee, B N; Hammill, H; Popek, E J et al. (2001) Production of interferons and beta-chemokines by placental trophoblasts of HIV-1-infected women. Infect Dis Obstet Gynecol 9:95-104 |
| Noroski, L M; Shearer, W T (1998) Screening for primary immunodeficiencies in the clinical immunology laboratory. Clin Immunol Immunopathol 86:237-45 |
| Lee, B N; Lu, J G; Shen, D Y et al. (1997) Quantification of IL-2 and IL-2 receptor mRNA in peripheral blood mononuclear cells by the RT-PCR based SHARP Signal system. Cytokines Cell Mol Ther 3:33-40 |
