PLACENTAL IMMUNOLOGY OF THE FIV-INFECTED CAT

描述：（摘自摘要）儿科艾滋病仍然是一个重要的 艾滋病流行病的一个组成部分，主要是由艾滋病毒的垂直传播造成的。 艾滋病。在美国，艾滋病毒感染的孕妇使用AZT， 降低了母婴传播率，但垂直传播 在不发达国家，AZT的使用率仍然很高， available.胎盘中产生许多免疫调节剂，包括细胞因子 以及通常参与维持妊娠的趋化因子。 成功妊娠需要精确调节免疫调节剂， 妊娠早期抑制炎性Th 1细胞因子。艾滋病毒感染 已知可改变受感染个体的细胞因子谱， 在HIV感染孕妇的滋养层细胞中， 妇女胎盘免疫学和艾滋病毒垂直传播是一个重要的 调查领域。猫免疫缺陷病毒（FIV）感染的猫是 一种公认的研究艾滋病的动物模型，包括垂直传播 由于FIV与HIV的遗传相关性以及FIV的生物学特性， 感染过程的相似性。因此，FIV感染的猫可能提供了一种 用于研究胎盘免疫学参数的有用模型， 易经胎盘传播。迄今为止， 猫胎盘免疫学和垂直传播FIV是完全 未经研究。该试点项目的目标是确定 开发这个模型系统。本研究的目的是：1和2） 确定所选炎性Th 1细胞因子的表达， b-趋化因子，并且趋化因子受体CXCR 4在FIV感染者和感染者之间存在差异 未感染猫的中期和足月胎盘。这些目标将 通过从胎盘细胞中分离RNA并使用逆转录酶来完成。 转译酶定量竞争性PCR（RT-qcPCR）程序进行定量 细胞因子和趋化因子的表达，并使用RT-PCR检测细胞因子和趋化因子的表达。 CXCR4 mRNA。3)为了评估FIV在胎盘细胞、胎儿组织、 和足月小猫以确定是否发生子宫内感染。这 将使用RT-qcPCR程序定量病毒 RNA在胎盘、胎儿和小猫中的表达，PCR检测FIV前病毒 在DNA样本中，和p26抗原检测以鉴定病毒表达。4)到 使用统计方法分析积累的数据，以确定是否 免疫调节剂的水平、病毒水平 表达和经胎盘传播。这个项目可能 确定一个重要的小动物模型，用于研究胎盘的作用， 免疫学在艾滋病毒垂直传播中的作用希望这个模型 提供一种方法来奠定知识的基础，这将有助于 制定基于免疫的干预战略，以消除这一重要的 HIV的机制。

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.