CMV Dynamics and Transmission Among Pregnant Women Living with HIV

项目总结 巨细胞病毒(CMV)是全球主要的先天性感染，造成巨大的 儿童听力损失和神经发育迟缓的负担。2000万名女性与 全球艾滋病毒(WLWH)比未感染艾滋病毒的妇女更有可能出现活跃的CMV复制 而且更有可能将CMV传播给每年出生的130万名感染艾滋病毒的婴儿。组合 全基因组的血清学和病毒学分析，该项目将使用现有的样本来新的工具 描述妊娠期间巨细胞病毒再感染和脱落的特征。我们还将探索特定的角色 导致母亲再感染和先天性或出生后婴儿感染的菌株之间的基因分型。 利用来自329名WLWH及其子女的现有纵向样本(在 孕期、分娩时和产后6周)，我们将解决以下具体目标： 1)使用新的血清学方法估计WLWH孕期CMV再感染的频率 方法：研究方法。 2)确定再感染与特定病毒株复制之间的联系 WLWH中的妊娠。 3)确定与传播给孕妇或其子女有关的基因类型特征。 血清学分析将使用传统的CMV毒株特异性抗体和新的 VirScan技术。VirScan允许使用噬菌体抗体库进行全面的血清学分析 我们已经适应了能够识别所有(&gt；10,000)测序CMV的所有抗体 菌株/变种。用定量聚合酶链式反应检测母婴唾液中的CMV 以及母体血液和阴道拭子。对聚合酶链式反应阳性的人进行CMV基因组分析 使用下一代测序技术和机器学习相结合的样本。这些菌株 将对孕妇中存在的病毒进行特征分析，并对传播给婴儿的病毒进行测序。 区分传播和非传播病毒的基因单核苷酸多态性 具有潜在功能意义的将被确定。统计分析将评估关联 CMV/HIV参数和相关结果之间的关系，包括母亲再感染和 先天性/后天感染。 从这个项目中获得的知识可能会导致预防性建议 基于新阐明的WLWH特有危险因素的孕产妇再感染，治疗 孕期再感染，预防先天感染。最后，这可能有助于减少 巨细胞病毒感染给感染艾滋病毒的家庭带来的巨大负担，通过告知 基因类型导致CMV传播，因此应包括在候选疫苗中。

PROJECT SUMMARY Cytomegalovirus (CMV) is the leading congenital infection globally, resulting in an enormous burden of childhood hearing loss and neurodevelopmental delay. The 20 million women living with HIV (WLWH) worldwide are more likely to have active CMV replication than women without HIV and are more likely to transmit CMV to the 1.3 million HIV-exposed infants born annually. Combining genome-wide serologic and virologic analyses, this project will use existing samples to new tools to characterize CMV reinfection and shedding during pregnancy. We will also explore the role of specific genotypes among strains causing maternal reinfection and congenital or postnatal infant infections. Leveraging existing longitudinal samples from 329 WLWH and their children (collected during pregnancy, at delivery, and until 6 weeks postpartum), we will address the following specific aims: 1) Estimate the frequency of CMV reinfection during pregnancy among WLWH using novel serologic methods. 2) Determine the association between reinfection and CMV replication of specific viral strains during pregnancy in WLWH. 3) Identify genotypic features associated with transmission to pregnant women or their children. Serological profiling will be done using traditional CMV strain-specific antibodies and novel VirScan technology. VirScan allows comprehensive serological profiling using a phage display library that we have adapted to be able to identify all antibodies to all (>10,000) sequenced CMV strains/variants. CMV shedding will be determined by quantitative PCR on maternal & infant saliva and maternal blood & vaginal swabs. CMV genomic analyses will be conducted on PCR positive samples using next-generation sequencing techniques combined with machine learning. The strains present in pregnant women will be characterized and those transmitted to infants will be sequenced. Single nucleotide polymorphisms in genes that distinguish transmitted from non-transmitted viruses with potential functional significance will be identified. Statistical analyses will evaluate associations between CMV/HIV parameters and outcomes of interest including maternal reinfection and congenital/postnatal infection. The knowledge gained from this project may result in preventative recommendations for maternal reinfections based on newly elucidated risk factors specific to WLWH, treatment for reinfection during pregnancy, and prevention of congenital infection. Finally, this may help to reduce the enormous burden of CMV infection on families affected by HIV, by informing which CMV genotypes result in CMV transmission and should therefore be included in candidate vaccines.