FIV MODEL OF IN UTERO HIV INFECTION AND INTERVENTION

本研究的目的是探讨发病机制 经胎盘猫免疫缺陷病毒（FIV）的传播作为一种 更好地了解产前母婴艾滋病毒感染指南 传输 3个具体目标是：（1）确定精确的 妊娠间隔期间病毒传播发生， 评估母体和病毒因素与胎儿风险相关的作用 感染，（2）确定组织嗜性和特定的胎盘， 胎儿细胞参与病毒传播，（3）比较菌株 FIV的垂直传播和非垂直传播， 阐明跨胎盘的菌株特异性因子 传代和胎儿感染性。 在目的1中，经胎盘的时机 FIV传播将通过评估感染流行率来确定 多个妊娠时间点的剖腹产胎儿率 代表了所有怀孕三个月。 统计相关性将是 在母体血液和免疫参数与循环之间寻求 病毒和组织前病毒载量，因为它们影响胎儿感染的风险。 在目的2中，将测定分离的整个组织的FIV感染。 对于鉴定为FIV嗜性的组织，特定细胞的感染性将 免疫组化和原代细胞 文化 在目标3中，感染FIV进化枝A和C同种型的猫将 评估其经胎盘传播病毒的能力。 如果 当病毒传播给胎儿时，组织和细胞的向性将被 目的1中使用的原型FIV-B-2542菌株， 已知会感染50%的胎儿上述研究将提供 与了解发病机制和干预有关的信息 HIV-1经胎盘传播

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.