FIV MODEL OF IN UTERO HIV INFECTION AND INTERVENTION

这项研究的目的是探讨致病机制。 经胎盘传播猫免疫缺陷病毒(FIV)作为一种 更好地了解产前母婴艾滋病毒-1指南 变速箱。三个具体目标是：(1)确定准确的 病毒传播发生的妊娠期和 评估母体和病毒因素在胎儿风险中的作用 感染，(2)确定组织取向和特定的胎盘和 参与病毒传播的胎儿细胞，以及(3)比较病毒株 垂直传播和非垂直传播的FIV 阐明导致交叉胎盘的菌株特异性因素 传代和胎儿传染性。在目标1中，经胎盘的时机 将通过评估感染流行率来确定FIV的传播 多个妊娠时间点剖宫产采集胎儿的比率 代表所有怀孕三个月的人。统计相关性将是 寻找母血与免疫学参数和循环之间的关系 病毒和组织前病毒载量影响胎儿感染风险。 在目标2中，将对分离的整个组织进行FIV感染的检测。 对于被鉴定为嗜FIV的组织，特定细胞的传染性将 由免疫组织化学菌株和原代细胞决定 文化。在AIM 3中，感染FIV A和C亚型的猫将 评估其经胎盘传播病毒的能力。如果 病毒会传播给胎儿，组织和细胞的嗜性会 根据目标1中使用的原型FIV-B-2542毒株进行确定 已知可感染约50%的胎儿。上述研究将提供 与了解发病机制和干预相关的信息 HIV-1经胎盘传播的可能性。

The objective of this research is to investigate pathogenetic mechanisms of transplacental feline immunodeficiency virus (FIV) transmission as a guide towards better understanding antenatal mother-to-infant HIV-1 transmission. The 3 specific aims are: (1) to determine the precise gestational interval during which virus transmission occurs and to assess the role of maternal and viral factors related to risk of fetal infection, (2) to identify tissue tropisms and specific placental and fetal cells involved in virus dissemination, and (3) to compare strains of FIV which are and are not vertically transmitted in order to elucidate strain-specific factors responsible for cross-placental passage and fetal infectivity. In aim 1, the timing of transplacental FIV transmission will be determined by assessing infection prevalence rates for cesarean-collected fetuses at multiple gestational time points representing all pregnancy trimesters. Statistical correlations will be sought between maternal blood and immunologic parameters and circulating viral and tissue proviral loads as they affect risk of fetal infection. In aim 2, dissociated whole tissues will be assayed for FIV infection. For tissues identified as FIV-tropic, infectivity of specific cells will be determined by immunohistochemical strains and by primary cell culture. In aim 3, cats infected with FIV clade A and C isotypes will be assessed for their ability to transmit virus transplacentally. If virus is transmitted to fetuses, tissue and cell tropisms will be determined as for the prototype FIV-B-2542 strain used in aim 1 which is known to infect about 50% of fetuses. The above studies will provide information pertinent to understanding the pathogenesis and intervention of transplacental HIV-1 transmission.