PLACENTAL IMMUNOLOGY OF THE FIV-INFECTED CAT

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DESCRIPTION: (Taken from Abstract) Pediatric AIDS remains an important component of the AIDS pandemic, resulting mainly from vertical transmission of HIV. The use of AZT by HIV-infected pregnant women in the U.S. has dramatically reduced the rate of maternal-fetal transmission, but vertical transmission rates remain very high in underdeveloped countries where the use of AZT is not available. Many immunomodulators are produced in placenta, including cytokines and chemokines that are normally involved in the maintenance of pregnancy. Successful pregnancy requires precise regulation of immunomodulators with suppression of inflammatory Th1 cytokines early in pregnancy. HIV infections are know to alter cytokine profiles in infected individuals, and Th1 cytokines were shown to be elevated in trophoblastic cells of HIV-infected pregnant women. Placental immunology and vertical transmission of HIV is an important area of investigation. The feline immunodeficiency virus (FIV)-infected cat is an accepted animal model for the study of AIDS, including vertical transmission of the virus, due to genetic relatedness of FIV to HIV and the biological similarities of the infection process. Thus, the FIV-infected cat may provide a useful model for the study of placental immunological parameters that may predispose transplacental transmission. To date, the relationship between feline placental immunology and vertical transmission of FIV is completely unstudied. The goal of this pilot project is to determine the feasibility of developing this model system. The objectives of this study are: 1 and 2) To determine whether the expression of selected inflammatory Th1 cytokines, b-chemokines, and the chemokine receptor CXCR4 differs between FIV-infected and uninfected cats in mid- and full-term placentae. These objectives will be accomplished by isolating the RNA from placental cells and using a reverse transciptase quantitative-competitive PCR (RT-qcPCR) procedure to quantitate expression of cytokines and chemokines and using RT-PCR to detect expression of CXCR4 mRNA. 3) To evaluate expression of FIV in placental cells, fetal tissues, and full term kittens to determine whether in utero infection occurs. This objective will be accomplished using an RT-qcPCR procedure to quantitate viral RNA expression in placentae, fetuses, and kittens, PCR to detect FIV provirus in DNA samples, and p26 antigen detection to identify virus expression. 4) To analyze the accumulated data using statistical methods to determine whether there is a correlation between levels of immunomodulators, levels of virus expression, and transplacental transmission in these animals. This project may identify an important small-animal model for the study of the role of placental immunology in the vertical transmission of HIV. Hopefully, this model will provide a means to lay a foundation of knowledge that will facilitate the development of immune-based intervention strategies to eliminate this important mechanism of HIV.