MECHANISMS OF VERTICAL TRANSMISSION OF HIV1

HIV1垂直传播机制

• 批准号: 2874204
• 负责人: Omar Bagasra
• 金额: $ 7.5万
• 依托单位: LINCOLN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2874204
• 关键词: amnion; embryo /fetus; female; genetic transcription; human immunodeficiency virus 1; human subject; newborn animals; perinatal; placenta; placental transfer; polymerase chain reaction; provirus; vertical transmission; virus DNA; virus load

Mother to child transmission of HIV-1 occurs in 15-40% of children born to HIV-1 seropositive mothers. It remains unclear why some others transmit HIV-1 to their infants while the majority do not. Studies to date indicate multiple factors associated with maternal-fetal transmission including plasma viremia, maternal immune response, maternal viral phenotypes, use of anti-retroviral agents during pregnancy, and obstetrical. Little is known of the mode of transmission or risk factors associated with transmission in utero. Identification of the role played by the placenta in maternal-fetal transmission of HIV-1 may lead to the development of strategies to prevent transplacental infection of the fetus. It is our hypothesis that: (i) the HIV-1 viral load is higher in the placentas of mothers with high plasma viremia during pregnancy resulting in higher rates of transmission; and (ii) early elimination of HIV-1 infected cells in the PBMCs of newborns results in long-term asymptomatic survivors whereas failure to do so results in the early manifestation of AIDS. In this application, we propose to (i) examine the correlation between PBMC/plasma viral burden during pregnancy and the viral burden of the placenta at the chorioamniotic layer at delivery; and (ii) examine the viral burden of the newborn at the time of delivery and throughout the first six months of life in correlation with the subsequent clinical development of HIV-1 related disease. 1. Determination of viral burden in maternal PBMCs and placental tissue. We will analyze the viral burden in: (i) circulating maternal PBMCs during pregnancy by determining the percentage of cells carrying proviral DNA by in situ DNA-PCR and viral burden by plasma quantitative branched chain DNA signal amplification. Further, we will determine the relative transcriptional activity of those infected cells by examination of HIV-1 specific RNA (spliced and unspliced) by reverse transcriptase in situ PCR, in situ hybridization, and branched chain DNA amplification. Similarly, (ii) we will analyze the viral burden within placental tissue from the corresponding mothers in conjunction with histologic typing within the various placental layers, especially at the chorioamnion. Finally, we will determine the origin (maternal versus fetal) of infected cells by simultaneous tissue typing of infected cells by in situ DNA PCR for HLA- DQA and HLA-DRB1 antigens. 2. Determination of viral burden in newborn PBMCs in relation to disease development. We will analyze cord blood, plasma as well as circulating PBMCs from the newborn to determine proviral burden and transcriptional activity of infected cells at the time of delivery as well as throughout the first nine months of life by the techniques outlined above. In addition, we will determine the origin of any infected cells by HLA typing as demonstrated above to explore the potential for transplacental egress of maternal cells into the fetal circulation as a mechanism of in utero transmission of infection. Finally, we will follow the level of proviral burden within the newborn to determine its correlation with subsequent disease progression. If such a correlation is established, these techniques may be used as a means of early diagnosis of infection in the newborn.

HIV-1儿童传播的母亲发生在15-40％的孩子中 HIV-1血清阳性母亲。 目前尚不清楚为什么其他人会发出 HIV-1给婴儿，而大多数人则没有。 迄今为止的研究 指示与母亲传播相关的多个因素 包括血浆病毒血症，母体免疫反应，母体病毒 表型，怀孕期间使用抗逆转录病毒药物以及 产科。 关于传输或风险因素的方式知之甚少 与子宫内传播有关。 识别扮演的角色 通过胎盘在母亲的传播中，HIV-1的传播可能会导致 制定防止移植感染的策略 胎儿。 我们的假设是：（i）HIV-1病毒载量更高 怀孕期间血浆病毒血症高的母亲的胎盘 导致更高的传输速率； （ii）早期消除 新生儿PBMC中的HIV-1感染细胞长期导致 无症状的幸存者，而未能这样做则导致早期 艾滋病的表现。 在此应用程序中，我们建议（i）检查 怀孕期间PBMC/血浆病毒负担之间的相关性与 递送时绒毛膜上的胎盘病毒负担；和 （ii）检查分娩时新生儿的病毒负担 在生命的前六个月中，与随后的 HIV-1相关疾病的临床发展。 1。确定母体PBMC和胎盘组织中的病毒负担。 我们将分析以下病毒负担：（i）在 通过确定携带病毒DNA的细胞百分比来怀孕 原位DNA-PCR和血浆定量分支链DNA的病毒负担 信号扩增。 此外，我们将确定亲戚 通过检查HIV-1的感染细胞的转录活性 逆转录酶原位PCR的特定RNA（剪接和未填充）， 原位杂交和分支链DNA扩增。 相似地， （ii）我们将分析从胎盘组织内的病毒负担 相应的母亲与组织学分类结合 各种胎盘层，尤其是在绒毛膜上。 最后，我们 将确定受感染细胞的原点（母体和胎儿） 通过原位DNA PCR与感染细胞的同时组织键入HLA- DQA和HLA-DRB1抗原。 2。确定新生儿PBMC的病毒负担与疾病有关 发展。 我们将分析脐带血，血浆以及循环 来自新生儿的PBMC以确定前病毒负担和转录 传递时感染细胞的活性 上面概述的技术的前九个月。 在 此外，我们将通过HLA键入确定任何受感染单元的起源 如上所述，探索了移植出口的潜力 母体细胞进入胎儿循环作为子宫内的机制 感染的传播。 最后，我们将遵循前病毒的水平 新生儿内的负担以确定其与后续的相关性 疾病进展。 如果建立了这样的相关性，这些 技术可以用作早期诊断感染的一种手段 新生。

项目成果

Protection against retroviruses are owing to a different form of immunity. An RNA-based molecular immunity hypothesis.

针对逆转录病毒的保护是由于不同形式的免疫。

• DOI: 10.1097/00129039-200006000-00008
• 发表时间: 2000
• 期刊: Applied immunohistochemistry & molecular morphology : AIMM
• 作者: Bagasra,O;Amjad,M
• 通讯作者: Amjad,M

Localization of human herpesvirus type 8 (HHV-8) in the Kaposi's sarcoma tissues and the semen specimens of HIV-1 infected and uninfected individuals by utilizing in situ polymerase chain reaction.

利用原位聚合酶链式反应对卡波西肉瘤组织以及 HIV-1 感染者和未感染者的精液样本中的人类疱疹病毒 8 型 (HHV-8) 进行定位。

• DOI: 10.1016/s0165-0378(98)00055-2
• 发表时间: 1998
• 期刊: Journal of reproductive immunology
• 影响因子: 3.4
• 作者: Bobroski,L;Bagasra,AU;Patel,D;Saikumari,P;Memoli,M;Abbey,MV;Wood,C;Sosa,C;Bagasra,O
• 通讯作者: Bagasra,O