Leveraging NICHD DASH biospecimens to isolate the effects of HIV infection and HIV exposure on epigenetic profiles in infants

利用 NICHD DASH 生物样本来分离 HIV 感染和 HIV 暴露对婴儿表观遗传特征的影响

• 批准号: 10161102
• 负责人: Stephanie Shiau
• 金额: $ 24.16万
• 依托单位: RBHS-SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-21 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10161102
• 关键词: Adaptive Immune System; Affect; Age; B-Lymphocytes; Behavior; Biometry; Birth; Blood; Blood specimen; Cell Maturation; Child; Cohort Studies; Consequences of HIV; Cytosine; DNA; DNA Methylation; Data; Environment; Epidemiology; Epigenetic Process; Exposure to; Face; Foundations; Genes; Genomics; Goals; Grant; Growth; Growth and Development function; Guanine; HIV; HIV Infections; HIV therapy; Health; Infant; Interdisciplinary Study; Intervention; Life; Life Cycle Stages; Link; Longitudinal Studies; Measures; Metabolic Diseases; Methylation; Morbidity - disease rate; Mother-to-child HIV transmission; Mothers; National Institute of Child Health and Human Development; Neurodevelopmental Deficit; New York City; Obesity; Outcome; Pattern; Perinatal; Perinatal Epidemiology; Personal Satisfaction; Population; Pregnancy; Pregnant Women; Regulation; Reporting; Research; Risk; Site; Specimen; Time; Work; aged; antiretroviral therapy; bead chip; blood-based biomarker; cohort; cost effective; epigenetic marker; epigenome; improved; in utero; innovation; inorganic phosphate; insight; neurodevelopment; offspring; pediatric human immunodeficiency virus; prevent; programs; prospective

PROJECT SUMMARY Children living with perinatally-acquired HIV infection (PHIV) as well as those exposed to HIV, but uninfected (HEU) face a lifetime of challenges to their health and well-being, including deficits in growth and neurodevelopment. There continue to be gaps in our understanding of how HIV infection and/or HIV exposure directly impact health at birth and throughout life. Filling these gaps is essential to define better interventions in these populations affected by HIV. Epigenetic analyses that can be non-invasively conducted on blood samples may offer tremendous opportunities to understand the mechanisms by which early HIV infection and HIV exposure affect long-term health. Our long-term goal is to identify easy-to-measure blood-based biomarkers that reflect HIV infection and/or HIV exposure and predict subsequent risk for morbidity in children affected by HIV as they grow and age throughout the life course. The objective of this grant is to characterize the independent effects of HIV infection and HIV exposure on epigenetic profiles in infants, and the contribution of these profiles to growth outcomes. Studies in contemporary populations are typically unable to disentangle the effects of HIV from the effects of antiretroviral therapy (ART) on DNA methylation profiles given the nearly complete use of ART today, yet understanding these independent effects is critical for defining mechanisms underlying long-term health consequences and potential points of intervention. This innovative and cost-effective project will leverage a wealth of historical data and blood biospecimens available in the NICHD Data and Specimen Hub (DASH) from the Mothers and Infants Cohort Study (MICS), a prospective, epidemiologic cohort study of pregnant women with and without HIV (n=450) and their offspring conducted in New York City between 1985-1991. Importantly, there was no ART use in the cohort. Our central hypothesis is that DNA methylation profiles in infants are directly subject to alteration by HIV infection and/or HIV exposure in the context of no ART, and these methylation profiles contribute to compromised growth reported in PHIV and HEU children. Our interdisciplinary research team is comprised of experts in pediatric HIV, epigenetics, infant growth and development, epidemiology, and biostatistics. We will employ state-of-the-art experimental and analytical approaches and utilize the comprehensive Illumina MethylationEPIC BeadChip array to characterize DNA methylation in stored blood biospecimens from MICS towards the following specific aims: 1) To examine the association between HIV infection/exposure and DNA methylation in infants at 3 and 12 months; 2) To evaluate the extent to which infant DNA methylation is associated with growth outcomes through 4 years in HIV-affected children. The research proposed in this exploratory R21 is significant because it will identify DNA methylation signatures of HIV infection and HIV exposure in infants and lay a foundation to further investigate the long-term health consequences of HIV-induced DNA methylation changes in a growing population affected by HIV. In addition, findings from this study may provide insight into other conditions affecting early life growth and development.

项目摘要 患有围产期获得艾滋病毒感染（PHIV）的儿童以及暴露于艾滋病毒的儿童，但未感染 （HEU）面临着对健康和福祉的一生，包括成长和 神经发育。我们对艾滋病毒感染和/或艾滋病毒如何暴露的理解继续存在差距 直接影响出生时和生命的健康。填补这些空白对于定义更好的干预措施至关重要 这些受艾滋病毒影响的人群。可以在血液样本上进行非侵入性的表观遗传分析 可能会提供巨大的机会来了解早期艾滋病毒感染和艾滋病毒的机制 暴露会影响长期健康。我们的长期目标是确定易于衡量的血液生物标志物 反映HIV感染和/或HIV暴露，并预测受HIV影响儿童发病的风险 随着它们在整个生活过程中的成长和年龄。这笔赠款的目的是表征独立的 艾滋病毒感染和艾滋病毒暴露对婴儿表观遗传特征的影响以及这些特征的贡献 增长结果。当代人口的研究通常无法解散艾滋病毒的影响 从抗逆转录病毒疗法（ART）对DNA甲基化轮廓的影响，几乎完全使用 今天的艺术，但是了解这些独立效应对于定义长期基础机制至关重要 健康后果和干预的潜在点。这个创新且具有成本效益的项目将利用 NICHD数据和标本中心（DASH）中可用的大量历史数据和血液生物测量 来自母亲和婴儿队列研究（MICS），这是一项前瞻性的流行病学研究孕妇 在1985年至1991年之间，有和没有艾滋病毒（n = 450）及其后代在纽约市进行。重要的是， 队列中没有艺术用途。我们的中心假设是婴儿的DNA甲基化谱直接 在没有艺术的情况下，受HIV感染和/或艾滋病毒暴露的改变，这些甲基化特征 在PHIV和HEU儿童中报告的增长造成了损害。我们的跨学科研究团队是 由小儿艾滋病毒，表观遗传学，婴儿成长与发育，流行病学和 生物统计学。我们将采用最先进的实验和分析方法，并利用 综合的光明甲基化甲基甲状腺芯片阵列以表征储存的血液中的DNA甲基化 从麦克风到以下特定目的的生物测量：1）检查艾滋病毒之间的关联 婴儿在3和12个月的婴儿中感染/暴露和DNA甲基化； 2）评估婴儿的程度 在受艾滋病毒影响的儿童中，DNA甲基化与4年的生长结果有关。研究 在此探索性R21中提出的意义很大，因为它将识别HIV感染的DNA甲基化特征 和艾滋病毒暴露于婴儿，并为进一步研究的长期健康后果奠定基础 艾滋病毒诱导的DNA甲基化变化受HIV影响的人群的变化。此外，从中的发现 研究可能会洞悉影响早期生活增长和发展的其他条件。