Pediatric AIDS is an important and poorly understood component of the AIDS problem in this country. Fundamental questions to be addressed are what periods during pregnancy are at risk of transmission and what characteristics of the maternal infection determine risk to the fetus/neonate. The pathogenesis of pediatric AIDS also appears to differ significantly from the adult HIV-1 infection. These factors plus the small size and immunological unknowns of infants make it difficult to apply knowledge on pathogenesis and therapeutic protocols developed in adults to pediatric AIDS. Utilizing the feline/FIV AIDS model that shows many similarities to HIV-1 infections (including pathogenesis and perinatal transmission) we hope to learn more of the mechanism of fetal/neonatal transmission and pathogenesis of pediatric AIDS. To address the question of FIV transmission, queens with acute, asymptomatic or symptomatic FIV infections will be bred and fetuses collected at midterm and late term by caesarean and evaluated for a) FIV provirus, mRNA, virus protein and infectious virus. Relevant tissues such as PBMC, thymus, lymph nodes and CNS will be examined. Fetuses will also be evaluated for pathology and developmental changes by histopathology, histochemistry, immunohistochemistry, and in situ hybridization. To study mode of transmission, placental tissues, amnion, cord blood and mammary tissues will be evaluated for FIV and Ab to FIV. Placental trophoblasts and Hofbauer cells/macrophages will be evaluated in culture for susceptibility to FIV infection. To evaluate the risk of neonatal transmission of FIV, we will perform cross-foster nursing experiments with normal and FIV infected queens and their respective neonates. Long term pathogenesis studies will be done on kittens infected as neonates (1-2 days of age) by monitoring FIV in PBMC (PCR, RT) and PBMC numbers (CD4+, CD8+ and B cells) and functions (neutralizing Ab, IL-1, IL2, T cell response to mitogens or Tc/Ts responses) as disease progresses to clinical AIDS. These observations will be correlated with clinical syndromes and complete virology, immunology and histopathology examinations of relevant tissues on subjects euthanized with advanced AIDS. These studies should provide important information on mechanism of perinatal transmission of FIV and the early pathogenic characteristics of the pediatric infection that determine disease progression.
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