NICHD Small Grants Programs--Perinatal HIV Transmission

NICHD 小额赠款计划——围产期艾滋病毒传播

• 批准号: 6653673
• 负责人: Felix O Aikhionbare
• 金额: $ 6.55万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653673
• 关键词: HIV infections; clinical research; disease /disorder proneness /risk; embryo /fetus tissue /cell culture; gene mutation; genetic markers; genetic polymorphism; histocompatibility gene; human fetus tissue; human genetic material tag; human tissue; immunogenetics; immunopathology; linkage disequilibriums; major histocompatibility complex; molecular cloning; nucleic acid sequence; pediatric AIDS; polymerase chain reaction; single strand conformation polymorphism; statistics /biometry; vertical transmission

DESCRIPTION (provided by applicant): Perinatal transmission accounts for more than 90 percent of HIV-infection in children. A thorough understanding of the molecular and genetics mechanisms of the host immune gene response (such as chemokines, cytokines, HLA polymorphisms) effecting the pathogens and transmission consequences of host-HIV-1 interactions is essential to all aspects of public health for diagnostic, transmission, and prevention strategies. This study is designed to understand the mutational role of HLA-G gene that make HIV-1 infected women more (or less likely) to transmit virus to her infant. HLA-G is non-classical class 1 MHC gene and it is highly expressed in extravillous cytotrophoblast at the maternal fetal interface. Specific aim: To further examine the potential role (s) of the mutation in HLA-G exon 2, which was previously associated to reduced risk in perinatal transmission (Aikhionbare, AIDS 2001,15: 2196-8) and any mutation(s) in HLA-G untranslated region in DNA samples obtained from both Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study (PACTS), for possibly increase or decrease in the susceptibility of a neonate to HIV-1- perinatal transmission. Approach: DNA samples will be obtained from HIV-1-infected and uninfected mother-child pairs followed as part of Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study will be screened by the following techniques: WAVETM Nucleic Acid Fragment Analysis, allele-specific polymerase chain reaction (PCR), single strand conformational polymorphism (SSCP), followed by DNA cloning/sequencing. Molecular data from this study will be subjected to Fisher's exact test, Maximum likelihood, Linked disequilibrum parameter, Odd ratio, Relative risk analysis to groups value. Results will furnish new insights into the basic mechanisms of the viral pathogenesis in AIDS, especially the contribution of certain host genetic factors to HIV-1 perinatal infection.

描述（由申请人提供）： 90% 以上的儿童 HIV 感染是由围产期传播造成的。 彻底了解宿主免疫基因反应（如趋化因子、细胞因子、HLA 多态性）影响病原体和宿主与 HIV-1 相互作用的传播后果的分子和遗传学机制，对于公共卫生诊断、传播的各个方面至关重要。 ，以及预防策略。 这项研究旨在了解 HLA-G 基因的突变作用，该基因使 HIV-1 感染女性更有可能（或更少可能）将病毒传播给婴儿。 HLA-G是非经典1类MHC基因，在母体胎儿界面的绒毛外细胞滋养层中高表达。 具体目标：进一步研究 HLA-G 外显子 2 突变的潜在作用，该突变先前与降低围产期传播风险相关（Aikhionbare, AIDS 2001,15: 2196-8）和任何突变位于从 Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote 获得的 DNA 样本中的 HLA-G 非翻译区科特迪瓦和围产期艾滋病合作传播研究 (PACTS)，旨在了解新生儿对 HIV-1 围产期传播的易感性可能增加或减少。方法：将从 HIV-1 感染和未感染的母子中获取 DNA 样本，作为 RETRO-C1 项目的一部分，01 BP 1712, 10 阿比让科特迪瓦和围产期艾滋病合作传播研究将通过以下方式进行筛选技术：WAVETM 核酸片段分析、等位基因特异性聚合酶链反应 (PCR)、单链构象多态性(SSCP)，然后进行 DNA 克隆/测序。本研究的分子数据将接受费舍尔精确检验、最大似然、连锁不平衡参数、奇数比、组值的相对风险分析。研究结果将为艾滋病病毒发病机制的基本机制提供新的见解，特别是某些宿主遗传因素对 HIV-1 围产期感染的贡献。